animal development

Introduction

 the processes that lead eventually to the formation of a new animal starting from cells derived from one or more parent individuals. Development thus occurs following the process by which a new generation of organisms is produced by the parent generation.

General features

Reproduction and development

      In multicellular animals (Metazoa), reproduction takes one of two essentially different forms: sexual and asexual. In asexual reproduction the new individual is derived from a blastema, a group of cells from the parent body, sometimes, as in Hydra and other coelenterates, in the form of a “bud” on the body surface. In sponges (sponge) and bryozoans (moss animal), the cell groups from which new individuals develop are formed internally and may be surrounded by protective shells; these bodies, which may serve as resistant forms capable of withstanding unfavourable environmental conditions, are released after the death of the parent. In certain animals the parent may split in half, as in some worms, in which an individual worm breaks into two fairly equal parts (except that the anterior half receives the mouth, “brain,” and sense organs if they are present).

      Obviously, in such a case it is impossible to say which of the two resulting individuals is the parent and which the offspring. Some brittle stars (brittle star) (starfish relatives) may reproduce by breaking across the middle of the body disk, with each of the halves subsequently growing its missing half and the corresponding arms.

      A common feature of all forms of asexual reproduction is that the cells (cell)—always a substantial number of cells, never only one cell—taking part in the formation of the new individual are not essentially different from other body, or somatic, cells. The number of chromosomes (bodies carrying the hereditary material) in the cells participating in the formation of a blastema is the same as in the other somatic cells of the parent, constituting a normal, double, or diploid (2n), set.

      In sexual reproduction, a new individual is produced not by somatic cells of the parent but by sex cells, or gametes, which differ essentially from somatic cells in having undergone meiosis, a process in which the number of chromosomes is reduced to one-half of the diploid (2n) number found in somatic cells; cells containing one set of chromosomes are said to be haploid (n). The resulting sex cells thus receive only half the number of chromosomes present in the somatic cell. Furthermore, the sex cells are generally capable of developing into a new individual only after two have united in a process called fertilization.

      Each type of reproduction—asexual and sexual—has advantages for the species. Asexual reproduction is, at least in some cases, the faster process, leading most rapidly to the development of large numbers of individuals. Males and females are independently capable of producing offspring. The large size of the original mass of living matter and its high degree of organization—the new individual inherits parts of the body of the parent: a part of the alimentary canal, for instance—make subsequent development more simple, and the attainment of a stage capable of self-support easier. New individuals produced by asexual reproduction have the same genetic constitution (genotype) as their parent and constitute what is called a clone. Though asexual reproduction is advantageous in that, if the parent animal is well adapted to its environment and the latter is stable, then all offspring will benefit, it is disadvantageous in that the fixed genotype not only makes any change in offspring impossible, should the environment change, but also prevents the acquisition of new characteristics, as part of an evolutionary process. Sexual reproduction, on the other hand, provides possibilities for variation among offspring and thus assists evolution by allowing new pairs of genes to combine in offspring. Since all body cells are derived from the fertilized egg cell, a mutation, or change, occurring in the sex cells of the parents immediately provides a new genotype in each cell of the offspring. In the course of evolution, sexual reproduction has been selected for, and established in, all main lines of organisms; asexual reproduction is found only in special cases and restricted groups of organisms.

Preparatory events

      In the case of multicellular animals we find there are two kinds of sex cells: the female sex cell ( ovum, or egg), derived from an oocyte (immature egg), and the male sex cell (spermatozoon or sperm), derived from a spermatocyte. Eggs are produced in ovaries; sperm, in testes. Both the egg and the sperm contribute to the development of the new individual; each providing one set of genes, thereby restoring the diploid number of chromosomes in the fertilized egg. The sperm possesses a whiplike tail (flagellum) that enables it to swim to the egg to fertilize it. In most cases the egg, a stationary, spherical cell, provides the potential offspring with a store of food materials, or yolk, for its early development. The term yolk does not refer to any particular substance but in fact includes proteins, phosphoproteins, lipids, cholesterol, and fats, all of which substances occur in various proportions in the eggs of different animals. In addition to yolk, eggs accumulate other components and acquire the structure necessary for the development of the new individual. In particular the egg acquires polarity—that is, the two ends, or poles, of the egg become distinctive from each other. At one pole, known as the animal pole, the cytoplasm appears to be more active and contains the nucleus (meiotic divisions occur in this region); at the other, called the vegetal pole, the cytoplasm is less active and contains most of the yolk. The general organization of the future animal is closely related to the polarity of the egg.

      When the amount of food reserve is comparatively small, as it is in many marine invertebrates and mammals (mammal) (in the latter the embryo is nourished by materials in the mother's blood), the egg may be barely visible to the unaided eye. The egg of the sea urchin is about 75 microns (0.003 inch) in diameter; that of a human being is slightly more than 0.1 millimetre. Eggs are classified according to the amount of yolk present. An egg with a small quantity of evenly distributed yolk is called an oligolecithal egg. One with more yolk that is unevenly distributed (i.e., concentrated towards the vegetal pole) is telolecithal; and one with still greater amounts of yolk in granules or in a compact mass is megalecithal.

      The egg is surrounded by protective membranes (membrane), which may be soft and jellylike or hard and calcified, like shells. Egg membranes are produced while the egg is either in the ovary or being carried away from the ovary in a tube called an oviduct. The eggs of many animals have both kinds of membranes. In insects (insect), a hard shell (chorion) forms around the eggs in the ovaries. In frogs, a very thin vitelline membrane forms around the eggs in the ovary; subsequently a layer of jelly is deposited around the eggs while they pass through the oviducts. In birds (bird), a very thin vitelline membrane is produced around the egg in the ovary; then several layers of secondary membranes are formed in the oviduct before the egg is laid. The outermost of these secondary membranes is the calcareous shell. In mammals the egg is surrounded by the so-called pellucid zone, which is equivalent to the vitelline membrane of other animals; follicle cells form an area called the corona radiata around this zone.

      After fertilization the egg, now called a zygote, is endowed with genes from two parents and has begun actual development. (Activation of the egg may be brought about by an agent other than sperm in certain animals, but such cases of parthenogenesis are exceptional.

      After fertilization, the zygote undergoes a series of transformations that bring it closer to the essential organization of the parents. These transformations, initiated at a physiological, perhaps even at a molecular, level, eventually result in the appearance of certain structures. The whole process is called morphogenesis (Greek morphē, “shape” or “form”; genesis, “origin” or “production”). The process of development is more easily understood if, at every step, the changes necessary to bring the system nearer the goal are considered. Depending on the achievements necessary at any step, development can be subdivided into a number of discrete phases, the first of which, cleavage, immediately follows fertilization.

Early development

embryo formation (embryology)

cleavage

      Since the goal of development is the production of a multicellular organism, many cells (cell) must be produced from the single-celled zygote. This task is accomplished by cleavage, a series of consecutive cell divisions. Cells produced during cleavage are called blastomeres. The divisions are mitotic (mitosis)—i.e., each chromosome in the nucleus splits into two daughter chromosomes, so that the two daughter blastomeres retain the diploid number of chromosomes. During cleavage, almost no growth occurs between consecutive divisions, and the total volume of living matter does not change substantially; as a consequence, the size of the cells is reduced by almost half at each division. At the beginning of cleavage, cell divisions tend to occur at the same time in all blastomeres, and the number of cells is doubled at each division. As cleavage progresses, the cells no longer divide at the same time.

      Cleavage in most animals follows an orderly pattern, with the first division being in the plane of the main axis of the egg. This cleavage plane is arbitrarily called vertical, on the assumption that the main axis of the egg is vertical. The second cleavage plane is again vertical but at right angles to the first, giving rise to four equal cells arranged around the main axis of the egg. The third cleavage plane is at right angles to both the first and second cleavage planes and is horizontal, or equatorial. Subsequent divisions may alternate between vertical and horizontal cleavage planes, but later cleavage divisions become randomly oriented. This pattern is typical of many animal groups; however, more complicated patterns of cleavage are found in such animals as annelids, mollusks, and nematodes.

      As the amount of yolk in the egg increases, it influences cleavage by hindering the cytoplasmic movements involved in mitosis. If there is only little yolk (oligolecithal eggs), the yolk granules follow the movements of the cytoplasm and are distributed in the resulting blastomeres. But if the amount of yolk is larger (megalecithal eggs), cleavages occur nearer the animal pole, where there is less yolk; as a result, the blastomeres nearer the animal pole are smaller than those nearer the vegetal pole. The presence of yolk masses may retard the onset of cleavage in a part of the egg or even suppress it altogether; in this case cleavage is partial, or meroblastic. Only a part of the egg material then is subdivided into cells, the rest remaining as a mass that serves as nourishment for the developing embryo.

      Cleavage is complete, or holoblastic, in many invertebrates including coelenterates, annelids, echinoderms, tunicates, and cephalochordates. The blastomeres may be either about equal or only slightly different in size. Cleavage in amphibians is holoblastic, but the size of the blastomeres is very uneven. Blastomeres are smallest at the animal pole and largest (and yolky) at the vegetal pole. Somewhat similar conditions prevail in many mollusks. In most fishes, birds, reptiles, and egg-laying mammals (monotremes), cleavage is discoidal—i.e., restricted to a disk of cytoplasm at the animal pole of the egg, most of the yolky egg material remaining uncleaved. Cleavage in insects and many other arthropods is superficial—i.e., the entire surface layer of egg cytoplasm subdivides into cells, and the egg contains a central mass of uncleaved yolk. The conditions of cleavage in placental mammals, including man, are peculiar.

      During cleavage, development involves only an increase of cell numbers; the shape of the embryo does not change, and chemical transformations within the embryo are restricted to those necessary for cell division. Chemical and structural transformations are concerned with accumulating chromosomal material in the nuclei of the blastomeres. Before each division the chromosomes (chromosome) carrying the genes double in number; this means that the chromosomal material, deoxyribonucleic acid (DNA), has to be synthesized. This synthesis proceeds possibly at the expense of cytoplasmic ribonucleic acid (RNA) but certainly also from simpler organic compounds. A certain amount of protein synthesis is also necessary for cleavage to proceed: if developing eggs are treated with puromycin, a substance which is known to suppress protein synthesis, cleavage stops immediately. The proteins concerned have not yet been identified. No proteins are synthesized, however, that would foreshadow the future differentiation of parts of the embryo. It is believed that the genes in the chromosomes remain largely inactive during cleavage. The rhythm (speed) of cleavage is wholly dependent on the cytoplasm of the egg.

      Although the shape and volume of the embryo do not change during cleavage, one important change in gross organization does take place. As the blastomeres are produced, they move outward, leaving a centrally located fluid-filled cavity. In cases of holoblastic cleavage, the blastomeres become arranged in a layer from one to several cells thick surrounding the cavity. The embryo at this stage may be likened to a hollow ball and is known as a blastula. The outer layer of cells is called the blastoderm, and the fluid-filled cavity the blastocoel. In discoidal cleavage the cells, which do not surround the whole embryo, lie only on the animal pole; nevertheless, a blastocoel may be formed by a crevice appearing between the blastomeres and the mass of yolk. The blastomeres then may be arranged as a saucer-shaped blastodisk covering the blastocoel.

      The formation of the blastula signifies the end of the period of cleavage. The next stage of development is concerned not with an increase in cell number, though cell divisions continue at a slower pace, but with rearrangement of the available cell masses to conform with the gross features of the future animal.

Gastrulation

      The embryo in the blastula stage must go through profound transformations before it can approach adult organization. An adult multicellular animal typically possesses a concentric arrangement of tissues of the body; this feature is common to all animal groups above the level of the sponges. Adult tissues are derived from three embryonic cell layers called germinal layers: the outer layer is the ectoderm, the middle layer is the mesoderm, and the innermost layer is the endoderm (entoderm). The ectoderm gives rise to the skin covering, to the nervous system, and to the sense organs. The mesoderm produces the muscles, excretory organs, circulatory organs, sex organs (gonads), and internal skeleton. The endoderm lines the alimentary canal and gives rise to the organs associated with digestion and, in chordates, with breathing.

      The blastula, which consists of only one cell layer, undergoes a dramatic reshuffling of blastomeres preparatory to the development of the various organ systems of the animal's body. This is achieved by the process of gastrulation, which is essentially a shifting or moving of the cell material of the embryo so that the three germinal layers are aligned in their correct positions.

      The rearrangement of the blastula to form the germinal layers is seen clearly in certain marine animals with oligolecithal eggs. The hollow blastula consists of a simple epithelial layer (the blastoderm), the transformation of which can be likened to the pushing in of one side of a rubber ball. As a result of such inpushing (or invagination), the spherical embryo is converted into a double-walled cup, the opening of which represents the position of the former vegetal pole. The involuted part of the blastoderm, lining the inside of the double-walled cup, gives rise to the endoderm and mesoderm, and the blastomeres remaining on the exterior become the ectoderm. As a consequence of the infolding at the vegetal pole, the blastocoel is reduced or obliterated, and a new cavity is created, the primitive gut cavity, or archenteron, which eventually gives rise to the hollow core (lumen) of the alimentary canal. At this stage the embryo has a primitive gut with an opening to the exterior and is known as a gastrula. The opening of the gastrula is the blastopore, or primitive mouth; both terms are somewhat misleading. It would seem that the term blastopore should be applied more appropriately to an opening in a blastula, in which, of course, no opening exists. As to the term primitive mouth, it must be pointed out that the blastopore does not always give rise to the adult mouth. In certain animal groups it becomes the anus, and a mouth forms as a completely new opening.

      In some coelenterates, cells at the vegetal pole do not form an invaginating pocket, but individual cells slide inward, losing connection with other cells of the blastoderm. Eventually these cells fill the blastocoel and form a compact mass of endoderm. The cavity (archenteron) within this mass and the opening (blastopore) to the exterior are then produced secondarily by the separation of these cells.

Amphioxus, echinoderms, and amphibians

      Gastrulation does not always proceed exactly as described above. In the course of evolution, certain animal groups have modified this critical stage of embryonic development, and these modifications have undoubtedly contributed to the successful continuation of species. In the primitive fishlike chordate amphioxus, for example, the invaginating blastoderm eventually comes into close contact with the inner surface of the ectoderm, thus practically squeezing the blastocoel out of existence or at least reducing it to a narrow crevice between the ectoderm and the endomesoderm. In echinoderms (echinoderm), on the other hand, a smaller portion of the blastoderm invaginates, and the blastocoel remains as a spacious internal cavity between the ectoderm and the endomesoderm. It persists as the primary body cavity and is the only body cavity (apart from the cavity of the alimentary canal) in such invertebrates as nematodes and rotifers.

      In the double-walled-cup stage, the two internal germinal layers—endoderm and mesoderm—may not yet be distinct. Their separation may occur later, in the second phase of gastrulation, by one of two methods. One is the development of outpocketings from the wall of the archenteron. In starfishes (sea star) and other echinoderms, the deep part of the endomesodermal invagination forms two thin-walled sacs, one on each side of the gastrula. These are the rudiments of the mesoderm; the remaining part of the archenteron becomes the endoderm and produces the lining of the gut. The cavities within the mesodermal sacs expand to become the coelom, the secondary body cavity of the animal. A somewhat similar process of mesoderm and coelom development occurs in amphioxus among the chordates, except that a series of mesodermal sacs forms on either side of the embryo, foreshadowing the segmented (metameric) structure common to chordates. Only the most anterior pairs of the mesodermal sacs actually contain a cavity at the time of their formation; the more posterior ones are solid masses of cells separating from the archenteric wall and from one another and developing coelomic cavities later.

      A second method of mesoderm formation is by the splitting off of mesodermal cells from the original common mass of endomesoderm. This may take the form of single cells detaching themselves from the archenteron or of whole sheets of cells splitting off from the endoderm. An example of the latter type is seen in the gastrulation of amphibians (amphibian). The development of specific regions of the early amphibian embryo—by the use of natural pigmentation or artificially introduced dyes—can be followed and their location in the adult recorded in diagrams called fate maps. The fate map of a frog blastula just prior to gastrulation demonstrates that the materials for the various organs of the embryo are not yet in the position corresponding to that in which the organs will lie in a fully developed animal. The endodermal material for the foregut, for example, lies not far from the vegetal pole; the ectodermal component of the mouth region (stomodeum) is situated close to the animal pole. Extensive rearrangement of the embryo is necessary to bring all the parts into their correct relationships.

      Because of the large amount of yolk and resulting uneven cleavage, gastrulation in amphibians cannot proceed by a simple infolding of the vegetal hemisphere. A certain amount of invagination does take place, assisted by an active spreading of the animal hemisphere of the embryo; as a result, the ectoderm covers the endodermal and mesodermal areas. The spreading is sometimes described as an “overgrowth”—an inappropriate term, since no growth or increase of mass is involved. The future ectoderm simply thins out, expands, and covers a greater surface of the embryo in a movement known as epiboly.

      Gastrulation in amphibians, in lungfishes (lungfish), and in the cyclostomes (cyclostome) (hagfishes and lampreys) begins with the formation of a pit on what will become the back (dorsal) side of the embryo. The pit represents the active shifting inward of the cells of the blastoderm. As these cells undergo a change in shape, there occurs also a contraction at the external surface, with adjacent cells being drawn toward the centre of the contraction even before an actual depression is formed. The cells most concerned in this process will become part of the future foregut. Further movement of the cells inward results in the formation of a distinct pit, which rapidly develops into a pocket-like archenteron with its opening, the blastopore. Once the archenteron is formed, more and more of the exterior cells roll over the edge of the blastopore and disappear into the interior. In the course of gastrulation the shape of the blastopore changes from a simple pit to a transverse slit and finally into a groove encircling the yolky material at the vegetal pole. As a result of epiboly of the animal hemisphere, the upper edge of the groove is gradually pushed down until the yolky cells of the vegetal pole are covered completely. The edges of the blastopore then converge toward the vegetal pole, the slit between them being eventually reduced to a narrow canal, which lies at the posterior end of the embryo and, in some species, becomes the anal opening. (In other cases the canal closes, and a new anal opening breaks through nearby, slightly more ventrally.)

      The cavity of the archenteron increases as more material from the outside is transferred inward, and the blastocoel becomes almost completely obliterated. Both mesoderm and endoderm are shifted into the interior, and only the ectoderm remains on the embryo surface. The mesoderm splits from the endoderm: the endoderm lines the archenteric cavity (and eventually becomes the lining of the alimentary canal), as the mesoderm surrounds the endoderm to form the chordamesodermal mantle. By the time the blastopore closes, the three germ layers are in their correct spatial relationship to each other.

Reptiles (reptile), birds (bird), and mammals (mammal)

      Although amphibian gastrulation is considerably modified in comparison with that in animals with oligolecithal eggs (e.g., amphioxus and starfishes), an archenteron forms by a process of invagination. Such is not the case, however, in the higher vertebrates that possess eggs with enormous amounts of yolk, as do the reptiles, birds, and egg-laying mammals. Cleavage in these animals is partial (meroblastic), and, at its conclusion, the embryo consists of a disk-shaped group of cells lying on top of a mass of yolk. This cell group often splits into an upper layer, the epiblast, and a lower layer, the hypoblast. These layers do not represent ectoderm and endoderm, respectively, since almost all the cells that form the embryo are contained in the epiblast. Future mesodermal and endodermal cells sink down into the interior, leaving only the ectodermal material at the surface. In reptiles, egg-laying mammals, and some birds, a pocket-like depression occurs in the epiblast but encompasses only chordamesoderm or even only the notochord. Individual cells of the remainder of the mesoderm and endoderm migrate into the interior and there arrange themselves into a sheet of chordamesoderm and of endoderm, the latter of which mingles with cells of the hypoblast if such a layer is present. The migration of the cells destined to form mesoderm and endoderm does not take place over the whole surface of the disk-shaped embryo but is restricted to a specific area along the midline. This area is more or less oval in reptiles and lower mammals; distinctly elongated in higher mammals and birds, it is called the primitive streak, a thickened and slightly depressed part of the epiblast that is thickest at the anterior end, called the Hensen's node.

      In animals having discoidal cleavage, the three germinal layers at the end of gastrulation are stacked flat; ectoderm on top, mesoderm in the middle, and endoderm at the bottom. The embryo is produced from the flattened layers by a process of folding to form a system of concentric tubes. The edges of the germ layers, which are not involved in the folding process, remain attached to the yolk and become the extra-embryonic parts; they are not directly involved in supplying cells for the embryo but break down yolk and transport it to the developing embryo.

      Higher mammals—apart from the egg-laying mammals—do not have yolk in their eggs but, having passed through an evolutionary stage of animals with yolky eggs, retain, particularly in gastrulation, features common to reptiles (and birds, which also had reptilian ancestors). As a result, at the end of cleavage the formative cells of the embryo—the cells that will actually build the body of the animal—are arranged in the form of a disk over a cavity that takes the place of the yolk of the reptilian ancestors of mammals. Within the disk of cells a primitive streak develops, and the three germinal layers are formed much as in many reptiles and birds.

      Gastrulation and the formation of the three germinal layers is the beginning of the subdivision of the mass of embryonic cells produced by cleavage. The cells then begin to change and diversify under the direction of the genes. The genes brought in by the sperm exert control for the first time; during cleavage all processes seem to be under control of the maternal genes. In cases of hybridization (hybrid), in which individuals from different species produce offspring, the influence of the sperm is first apparent at gastrulation: paternal characteristics may appear at this stage; or the embryo may stop developing and die if the paternal genes are incompatible with the egg (as is the case in hybridization between species distantly related).

      The diversification of cells in the embryo progresses rapidly during and after gastrulation. The visible effect is that the germinal layers become further subdivided into aggregations of cells that assume the rudimentary form of various organs and organ systems of the embryo. Thus the period of gastrulation is followed by the period of organ formation, or organogenesis.

Embryonic adaptations

      Throughout its development the embryo requires a steady supply of nourishment and oxygen and a means for disposal of wastes. These needs are met in various ways, depending in particular on (1) whether the eggs develop externally (oviparity), are retained in the maternal body until ready to hatch (ovoviviparity), or are carried in the maternal body to a later stage (viviparity); and (2) the length of embryonic development.

Adaptations in animals other than mammals

      Eggs of many marine invertebrates are discharged directly into water, and the period of development before the larva emerges is relatively brief. Oxygen diffuses easily into the small eggs, and nourishment is provided by a moderate amount of yolk. During cleavage the yolk is distributed to all the blastomeres. Much of the nourishment in the egg is stored as animal starch, or glycogen, which is almost completely used by the time the larva emerges from the egg. A small amount of water and inorganic salts are taken in by the embryo from surrounding seawater. Eggs developing in freshwater carry their own supply of necessary amounts of certain salts that are not present in sufficient quantities in the environment. Products of metabolism—especially carbon dioxide and nitrogenous wastes in the form of ammonia—diffuse out from small embryos developing in water.

      The eggs of terrestrial animals must overcome the hazard of drying. In certain species this danger is avoided because the animal returns to water to breed, such as frogs and salamanders. Some groups of insects (e.g., dragonflies, mayflies, and mosquitoes) also lay eggs in water, and the larvae are aquatic. Eggs of other animals (e.g., snails, earthworms) are laid in moist earth and thus are protected from drying up. In terms of evolution, however, a decisive solution to the problem of development on land was arrived at by most insects and by reptiles and birds, which developed eggs with a shell impermeable to water or, at least, resistant to rapid evaporation. The shells of bird and insect eggs, while restricting evaporation of water, allow oxygen to diffuse into the egg and carbon dioxide to diffuse out. Apart from gas exchange, the eggs constitute closed systems, which give nothing to the outside and require nothing from it. Such eggs are called cleidoic. Because the products of nitrogen metabolism in cleidoic eggs cannot pass through the eggshell, animals (birds and insects) have had to evolve a method of storing wastes in the form of uric acid, which, since it is insoluble, is nontoxic to the embryo.

      After a short period of development in the egg, the emerging young animal has to fend for itself, unless there is some form of parental care. Exposure to the external environment at a tender age results frequently in loss of life, a hazard met by many animals through an increase in the supply of nourishment within the egg, thus allowing the young to attain a greater size and development. This tendency to produce large yolky eggs has been achieved independently in different evolutionary lines: in octopuses and squids among the mollusks, in sharks among the fishes, and in reptiles and birds among the terrestrial vertebrates.

      As has been indicated, cleavage is incomplete in eggs with large amounts of yolk. Although some yolk platelets may be enclosed in the formative cells of the embryo, the bulk of the yolk remains an uncleaved mass, overgrown and surrounded by the cellular part of the embryo. In such cases a membranous bag, or yolk sac, is formed and remains connected to the embryo by a narrow stalk (the evolutionary precursor of the umbilical cord of mammals). The cellular layers surrounding the yolk sac and forming its walls may consist of all three germinal layers (in reptiles and birds), so that the yolk virtually comes to lie inside an extension of the gut of the embryo; or (in bony fishes) the yolk sac may be enclosed in layers of ectoderm and mesoderm. In either case a network of blood vessels develops in the walls of the yolk sac and transports the yolk products to the embryo. As the yolk is broken down and utilized, the yolk sac shrinks and is eventually drawn into the body of the embryo. In addition to the yolk sac, extra-embryonic parts are also encountered in the form of embryonic membranes, which are found in higher vertebrates and in insects. Vertebrates have three embryonic membranes: the amnion, the chorion, and the allantois.

      In reptiles, birds, and mammals, folds develop on the surface of the yolk sac just outside and around the body of the embryo proper. These folds, consisting of extra-embryonic ectoderm and extra-embryonic mesoderm, rise up and fuse dorsally, enclosing the embryo in a double-lined, fluid-filled chamber known as the amniotic cavity. The inner lining of the fold becomes the amnion, and the outer becomes the chorion, which ultimately surrounds the entire embryo. The amniotic fluid protects the embryo from drying, prevents the adhesion of the embryo to the inner surface of the shell, and provides the embryo with efficient shock absorption against possible damaging jolts. (The aminion and chorion develop in the same way in insect embryos.) The third membrane, or allantois, is originally nothing more than the urinary bladder of the embryo. It is a saclike growth of the floor of the gut, into which nitrogenous wastes of the embryo are voided. It enlarges greatly during the course of development, eventually expanding between the amnion and chorion and also between the chorion and the yolk sac, to become the third embryonic membrane. In addition to providing storage space for the nitrogenous wastes of the embryo, the allantois takes up oxygen, which penetrates into the egg from the exterior, and delivers it, by way of a network of blood vessels, to the embryo.

Adaptations in mammals

      At some early stage during the evolution of viviparous (viviparity) mammals, eggs came to be retained in the oviducts of the mother. The embryo then was provided with nourishment from fluids in the oviduct; the yolk, which became redundant, gradually ceased to be provided, and the eggs became oligolecithal. The eggshell, present in reptiles, was no longer needed and eventually disappeared, as did the white of the egg. The chorion, however, remained as the most external coat of the developing embryo through which nourishment reaches the embryo. It acquired the ability to adhere closely to the walls of the uterus (which was what that part of the oviduct holding the embryo had become) and became the so-called trophoblast. The blood-vessel network of the underlying allantois conveys nutrients that diffuse through the trophoblast to the body of the embryo proper. These modifications gave rise to a new organ, the placenta, formed from tissues of both the mother and the embryo: the uterine wall with its blood vessels provided by the mother; the trophoblast and allantois—and in some mammals also the yolk sac—with their blood vessels provided by the embryo.

      The overall development of placental mammals as a result of these changes is profoundly different from that of their ancestors, the reptiles (reptile), and proceeds in the following way: the tiny yolkless egg is fertilized in the upper portion of the oviduct by sperm received from the male in the process of coupling (coitus); cleavage starts as the egg is propelled slowly down the oviduct by action of cilia in the oviduct lining. At the end of cleavage a solid ball of cells called a morula is produced. The surface cells of the morula become the trophoblast and the inner cell mass gives rise to the embryo (the formative cells) and also its yolk sac, amnion, and allantois. A cavity appears within the morula, converting it into a hollow embryo, called the blastocyst. This cavity resembles the blastocoel but, in fact, is analogous to the yolk sac of meroblastic eggs, except that there is no yolk and the cavity is filled with fluid. At the blastocyst stage, the embryo enters the uterus and attaches itself to the uterine wall. This attachment, or implantation, a crucial step in the development of a mammal, is attained through the action of the trophoblast, which forms extensions, known as villi, that penetrate the uterine wall. In higher placental mammals, the lining of the uterine wall and, in varying degrees, the underlying tissues as well are partially destroyed, resulting in a closer relationship between the blood supplies of the mother and the embryo. Indeed, in man and in some rodents, the blastocyst sinks completely into the uterine wall and becomes surrounded by uterine tissue.

      While implantation takes place, the formative cells arrange themselves in the form of a disk under the trophoblast. In the disk, the germinal layers develop much as in birds (bird), with the formation of a primitive streak and migration of the chordamesoderm into a deeper layer. A layer of endoderm is formed adjoining the cavity of the blastocyst, and an amniotic cavity develops, enclosing the embryo; in lower placental mammals, the allantois also develops. The embryo proper, lying in the amniotic cavity, is connected to the extra-embryonic parts by the umbilical cord. The umbilical cord lengthens greatly during later development. In higher mammals, the cavity of the allantois is reduced, but the allantoic blood vessels become well developed and extend through the umbilical cord, connecting the embryo to the placenta. The blood that circulates in the placenta brings oxygen and nutrients from the maternal blood to the embryo and carries away carbon dioxide and other waste products from the embryo to the maternal blood for disposal by the maternal body.

      Although tissues of maternal and embryonic origin are closely apposed in the placenta, there is little actual mingling of the tissues. Despite an occasional penetration of an embryo cell into the mother and vice versa, there is a placental barrier between the two tissues. The blood circulation of the mother is at all times completely separated from that of the embryo and its extra-embryonic parts. The placental barrier, however, does allow molecules of various substances to pass through; such differential permeability is indeed necessary if the embryo is to obtain nourishment. The permeability of the placental barrier differs in different animals; thus antibodies, which are protein molecules, may penetrate the placental barrier in man but not in cattle.

      The maintenance of the fetus—as the more advanced embryo of a mammal is called—in the uterus is under hormonal control. In the initial stages of pregnancy, the continued existence of the embryo in the uterus depends on the hormone progesterone, which is secreted by the corpora lutea, “yellow bodies,” that develop in the ovary after an egg has been released.

      At birth the fetal parts of the placenta separate from the maternal parts. Contraction of the uterine wall first releases the fetus from the uterus; the fetal parts of the placenta (the afterbirth) follow. In certain cases of intimate connection between fetal and maternal tissues, the maternal tissues are torn, and birth is accompanied by profuse bleeding.

organ formation

Primary organ rudiments

      Immediately after gastrulation—and sometimes even while gastrulation is underway—the germinal layers begin subdividing into regions that will give rise to various parts of the body. Subdivision proceeds in stages: initially a mass of cells is set aside for an organ system (for the alimentary canal, for instance) and subsequently further subdivided into the rudiments of various parts of the organ system, such as the liver, stomach, and intestines. The initially formed larger units are referred to as primary organ rudiments; those they later give rise to, as secondary organ rudiments.

Differentiation of the germinal layers

      The type of organ rudiment produced depends on the organization of the body in any particular group in the animal kingdom. In the vertebrates the earliest subdivision within a germinal layer is the segregation within the chordamesodermal mantle of the rudiment of the notochord from the rest of the mesoderm. During gastrulation the material of the notochord comes to lie middorsally in the roof of the archenteron. It separates by longitudinal crevices from the chordamesodermal mantle lying to the left and right. The material of the notochord then rounds off and becomes a rod-shaped strand of cells immediately under the dorsal ectoderm, stretching from the blastopore toward the anterior end of the embryo, to the midbrain level. In front of the tip of the notochord, there remains a thin sheet of prechordal mesoderm.

      The mesodermal layer adjoining the notochord becomes thickened and, by transverse crevices, subdivided into sections called somites (somite). The somites, which later give rise to the segmented body muscles and the vertebral column, are the basis of the segmented organization typical of vertebrates (seen especially in the lower fishlike forms but also in the embryos of higher vertebrates). The lateral and ventral mesoderm, which remains unsegmented, is called the lateral plate. The somites remain connected to the lateral plate by stalks of somites that play a particular role in the development of the excretory (nephric) system in vertebrates; for this reason they are called nephrotomes. Rather early the mesodermal mantle splits into two layers, the outer parietal (somatic) layer and the inner visceral (splanchnic) layer, separated by a narrow cavity that will expand later to form the coelomic, or secondary, body cavity. The coelomic cavity extends initially through the nephrotomes into the somites; in the somites it is eventually obliterated. Endoderm completely surrounds the lumen of the archenteron (when present) and produces the cavity of the alimentary canal. If no archenteric cavity is formed during gastrulation, the cavity of the alimentary canal is formed by the separation of cells in the middle of the mass of endoderm (as in bony fishes) or by folding of the sheet of endoderm. The endodermal gut sooner or later acquires an extended anterior part called the foregut and a narrower and more elongated posterior part, the hindgut. Characteristic of chordates is the development of the nervous system from a part of ectoderm lying originally on the dorsal side of the embryo, above the notochord and the somites. This part of the ectodermal layer thickens and becomes the neural plate, whose edges rise as neural folds that converge toward the midline, fuse together, and form the neural tube. In vertebrates the neural tube lies immediately above the notochord and extends beyond its anterior tip. The neural tube is the rudiment of the brain and spinal cord; (spinal cord) its lumen gives rise to the cavities, or ventricles, of the brain and to the central canal of the spinal cord. The remainder of the ectoderm closes over the neural tube and becomes, in the main, the covering layer (epithelium) of the animal's skin (epidermis). As the neural tube detaches itself from the overlying ectoderm, groups of cells pinch off and form the neural crest, which plays an important role in the development of, among other things, the segmental nerves of the brain and spinal cord.

      In developing the primary organ rudiments mentioned above, the embryo acquires a definite organization clearly recognizable as that of a chordate animal. Similar processes, which occur in the development of other animals, establish the basic organization of an annelid, a mollusk, or an arthropod.

Embryonic induction

      The organization of the embryo as a whole appears to be determined to a large extent during gastrulation, by which process different regions of the blastoderm are displaced and brought into new spatial relationships to each other. Groups of cells that were distant from each other in the blastula come into close contact, which increases possibilities for interaction between materials of different origin. In the development of vertebrates in particular, the sliding of cells (presumptive mesoderm) into the interior and their placement on the dorsal side of the archenteron (in the archenteric “roof”), in immediate contact with the overlying ectoderm, is of major importance in development and subsequent differentiation. Experiments have shown that, at the start of gastrulation, ectoderm is incapable of progressive development of any kind; that only after invagination, with chordamesoderm lying directly underneath it, does ectoderm acquire the ability for progressive development. The dorsal mesoderm, which later differentiates into notochord, prechordal mesoderm, and somites, causes the overlying ectoderm to differentiate as neural plate. Lateral mesoderm causes overlying ectoderm to differentiate as skin. The influence exercised by parts of the embryo, which causes groups of cells to proceed along a particular path of development, is called embryonic induction. Though induction requires that the interacting parts come into close proximity, actual contact is not necessary. The inducing influence—whatever it might be—is a diffusible substance emitted by the activating cells (the inductor). The inducing substance of the mesoderm is a large molecule, probably a protein or a nucleoprotein, which presumably penetrates reacting cells, though direct and unequivocal proof of such penetration is still unavailable. Inducing substances are active on vertebrates belonging to many different classes; e.g., inductions of primary organs have been obtained by transplanting mammalian tissues into frog embryos or by transplanting tissues of a chick embryo into the embryo of a rabbit.

      Induction is responsible not only for the subdivision of ectoderm into neural plate and epidermis but also for the development of a large number of organ rudiments in vertebrates. The notochord is a source of induction for the development of the adjoining somites and nephrotomes; the latter appear jointly to induce development of limb rudiments from the lateral plate mesoderm. Further examples are mentioned below in connection with development of the various organs.

      Since the results of induction are different for different organ rudiments, it must be presumed that there exist inducing substances with specific action, at least to a certain extent; thus, the lateral mesoderm induces differentiation of the skin but not neural plate from the very same kind of ectoderm. The number of inducing substances need not, however, be the same as the number of different kinds of tissues and organs, since certain differentiations could possibly be induced by a combination of two or more inducing substances, or the same inducing substance might have different effects on different tissues. It has been suggested that the regional organization of the entire vertebrate body could be controlled by the graded distribution of only two inducing substances—provisionally named the neuralizing substance and the mesodermalizing substance—along the length of the embryo. The neuralizing substance, concentrated at the anterior end, gradually decreases toward the posterior end; the mesodermalizing substance, on the other hand, is concentrated at the posterior end and decreases toward the anterior end. The differentiation of induced structures depends on the relative amounts of the two inducing substances at any given point in the embryo. Acting alone, the neuralizing substance induces only nervous tissue, which takes the form of the forebrain, and the mesodermalizing substance induces only mesodermal structures (e.g., somites, notochord).

      In the amphibian embryo, induction appears to have its primary source in the dorsal lip of the blastopore, which eventually gives rise to the notochord and adjoining somites. Induction by the notochord and somites is responsible for the development of the neural plate in the ectoderm, of lateral and ventral parts of the mesodermal mantle, and of the lumen of the alimentary canal in the endoderm. The dorsal lip of the blastopore for this reason has been called the primary organizer. In higher vertebrates, in which gastrulation occurs through the medium of a primitive streak, the anterior end of the streak and the Hensen's node have properties similar to those of a primary organizer. Organization centres have been found, or suspected, in embryos of animals belonging to a few other groups, in particular the insects and sea urchins, but the interpretation of the experimental results in these animals is less satisfactory than in the case of vertebrates.

      The concept of an organization centre suggests that a part of the embryo differs from the rest of the embryonic tissues in being more active. The more active parts of the embryo (and also of animals in later stages of development) are particularly sensitive to certain noxious influences in their environment. If an embryo is deprived of oxygen or subjected to weak concentrations of poisons (poison), the first parts to suffer are the most morphogenetically active ones. In vertebrate embryos the anterior end of the head is most sensitive. Early sea-urchin embryos have two centres of maximal sensitivity: one at the animal pole and the other at the vegetal pole. The damage (malformation) done by noxious influences may result in actual breakdown of cells in a region of maximal sensitivity and may also lead to a depression of the developmental potential of the cells. Thus, the graded distribution of certain physiological properties appears to play a part in morphogenetic processes: physiological gradients are in fact also morphogenetic gradients.

      Gradients in the embryo can be used to control development to a certain extent, by exposing the embryo to influences that, while reaching all parts, have a local effect as the result of differences in sensitivity. Disturbances of normal development often are the result of disruptions of gradients.

organogenesis and histogenesis

      The primary organ rudiments continue to give rise to the rudiments of the various organs of the fully developed animal in a process called organogenesis. The formation of organs, even those of diverse function, shares some common features, which are considered in this section. As the organs form, so do their component tissues, in a process termed histogenesis.

      A germinal layer, as the name implies, is a sheet of cells. An organ rudiment may be formed and separated from such a sheet in several ways. A groove, or fold, may appear within the layer, become closed into a tube, and then separated from the original layer. A tube once formed may be subdivided into sections by constrictions and dilations of the tube at certain points. This is the way the nervous system rudiment is formed in vertebrates as already described.

      Alternatively, the germinal layer may produce a round depression, or pocket. The pocket may then separate from the layer as a vesicle, or it may elongate and branch at the tip while still connected with the layer. The latter method is common in the development of various glands and also the lungs in vertebrates.

      Still another method of rudiment formation in a germinal layer is by the development of local thickenings, elongated or round, and detachment from the epithelial sheet. If a lumen appears later within such a body, the result may be the same as that achieved by folding—that is, a tube or vesicle may be formed. Indeed, the same sort of organ may develop even in related animals in either of these ways. The epithelial layer may further be cut up into segments, with the layer losing continuity, as in the formation of somites in vertebrates or similar mesodermal blocks in segmented invertebrates (e.g., annelids and arthropods).

      Lastly, the cells of a germinal layer may give up their connection to each other and become a mass of loose, freely moving cells called embryonic mesenchyme. This mass gives rise to various forms of connective tissue but may also condense into more solid structures, including parts of the skeleton and the muscles.

      Many organs are comprised of all three germinal layers. It is very common for glands, for instance, to derive their lining from an ectodermal or endodermal epithelium and their connective tissue (sometimes in the form of a capsule) from mesenchyme of mesodermal origin. Parts of ectoderm and endoderm cooperate also in the development of the lining of the alimentary canal, and mesoderm provides the connective tissue and muscular sheath of the canal.

      In this section the development of organs of the body are dealt with according to the germinal layer that contributes the most important part, and only the development of vertebrate organs is considered.

Ectodermal derivatives

The nervous system

      The vertebrate nervous system develops from the neural plate—a thickened dorsal portion of the ectoderm—which forms a tube, as described earlier. From the very start the tube is wider anteriorly, the end that gives rise to the brain. The posterior part of the neural tube, which gives rise to the spinal cord, is narrower and stretches as the embryo lengthens. Stretching involves the head to only a very minor degree.

The brain and spinal cord

      Constrictions soon appear in the brain region of the neural tube, subdividing it into three parts, or brain vesicles, which undergo further transformations in the course of development. The most anterior of the primary brain vesicles, called the prosencephalon, gives rise to parts of the brain and the eye rudiments. The latter appear in a very early stage of development as lateral protrusions from the wall of the neural tube, which are constricted off from the remainder of the brain rudiment as the optic vesicles. The rest of the prosencephalon constricts further into two portions, an anterior one, or telencephalon, and a posterior one, or diencephalon. The telencephalon gives rise, in lower vertebrates, to the smell, or olfactory, centre; in higher vertebrates and man, it becomes the centre of mental activities. The diencephalon, with which the eye vesicles are connected, was presumably originally an optic centre, but it has acquired, in the course of evolution, a function of hormonal regulation. The floor of the diencephalon forms a funnel-shaped depression, the infundibulum, which becomes connected with the pituitary, or hypophysis (pituitary gland), the most important gland of internal secretion (i.e., endocrine (endocrine system) gland) in vertebrates. Indeed, the posterior lobe of the hypophysis is actually derived from the floor of the diencephalon. Tissues of the infundibulum and the posterior lobe of the hypophysis produce certain hormones (oxytocin and vasopressin) and stimulate the production and release of other hormones from the anterior lobe of the hypophysis.

      The second primary brain vesicle, the mesencephalon, gives rise to the midbrain, which, in higher vertebrates, takes part in coordinating visual and auditory stimuli.

      The third primary brain vesicle, the rhombencephalon, is more elongated than the first two; it produces the metencephalon, which gives rise to the cerebellum with its hemispheres, and the myelencephalon, which becomes the medulla oblongata. The cerebellum acts as a balance and coordinating centre, and the medulla controls functions such as respiratory movements.

      The cells constituting the wall of the neural tube and, later, of the brain and spinal cord become arranged in such a way that they point into the central cavity of the tube. The differentiation of nervous tissue involves many cells abandoning their connection to the inner surface of the neural tube and migrating outward, where they accumulate as a mantle. The first cells to migrate become the neurons (neuron), or nerve cells. They produce outgrowths called axons (axon) and dendrites, by which the cells of the nervous system establish communication with one another to form a functional network. Some of the outgrowths extend beyond the confines of the brain and spinal cord as components of nerves; they establish contact with peripheral organs, which thus fall under the control of the nervous system. Cells migrating from the inner surface of the neural tube later in development become astrocytes, which are the supporting elements of nerve tissue.

      The fate of nerve cells is dependent largely on whether they succeed, directly or indirectly (through other neurons), in connecting with peripheral organs. Nerve cells that fail to establish connections die. Thus, if in early stages of embryonic development, some organ, a limb rudiment for instance, is surgically removed, the nerve cells in the centres supplying nerves to such an organ are reduced in number, and the corresponding nerves also diminish or disappear. On the other hand, if an organ is introduced by transplantation into a developing embryo, the organ will be supplied by nerves from a nerve centre in which the number of cells apparently increases; no additional cells are provided, but cells that would otherwise have degenerated remain active and differentiate into functional neurons, thus satisfying the demand created by the additional organ.

      Nerves do not consist entirely of outgrowths of neurons located in the brain and spinal cord. Many components of nerves are outgrowths of neurons, the cell bodies of which are located in masses called ganglia; (ganglion) there are three main types of ganglia: spinal ganglia, cranial ganglia, and ganglia of the autonomous nervous system. The spinal ganglia are derived from cells of the neural crest—the loose mesenchyme-like tissue that remains between the neural tube and skin after separation of the two. Part of the cells of the neural crest in the region of the trunk and tail accumulate in segmental groups (corresponding to the mesodermal somites) and provide fibres to peripheral organs and to the spinal cord. These fibres constitute the sensory pathways in the spinal nerves. The motor components of the spinal nerves—fibres that activate muscles—are outgrowths of neurons lying in the spinal cord. The ganglia of the cranial nerves are produced only in part from cells of the neural crest; an additional component comes from the epidermis on the side of the head. Cells of the epidermal thickenings called placodes detach themselves and contribute to the formation of the cranial ganglia and thus of the cranial nerves.

      The ganglia of the autonomous (sympathetic) nervous system are derived, as are the spinal ganglia, from neural-crest cells, but, in this case, the cells migrate downward to form groups near the dorsal aorta, near the intestine, and even in the intestinal wall itself. The outgrowths of cells in these ganglia are the nerve fibres of the sympathetic nerves (see also nervous system, human: The autonomic nervous system (nervous system, human)).

Major sense organs

The eye (eye, human)

      As has been pointed out, the rudiments of the eyes develop from optic vesicles, each of which remains connected to the brain by an eye stalk, which later serves as the pathway for the optic nerve. The optic vesicles extend laterally until they reach the skin, whereupon the outer surface caves in so that the vesicle becomes a double-walled optic cup. The thick inner layer of the optic cup gives rise to the sensory retina of the eye; the thinner outer layer becomes the pigment coat of the retina. The opening of the optic cup, wide at first, gradually becomes constricted to form the pupil, and the edges of the cup surrounding the pupil differentiate as the iris. The refractive system of the eye and, in particular, the lens of the eye are derived not from the cup but from the epidermis overlying the eye rudiment. When the optic vesicle touches the epidermis and caves in to produce the optic cup, the epidermis opposite the opening thickens and produces a spherical lens rudiment. The lens develops by an induction by the optic vesicle on the epidermis with which it comes in contact. A further influence emanating from the eye changes the epidermis remaining in place over the lens into a transparent area, the cornea. Influence of the optic cup on the surrounding mesenchyme causes the latter to produce a vascular layer around the retina and, outside of that, a tough fibrous or (in some animals) even a partly bony capsule called the sclera. Thus a complex interdependence of different materials produces the fully developed and functional vertebrate eye.

The ear (ear, human)

      The main part of the ear rudiment is derived from thickened epidermis adjoining the medulla. This area of the epidermis invaginates to produce the ear vesicle, which separates from the epidermis but remains closely apposed to the medulla. The ear vesicle becomes complexly folded to produce the labyrinth (inner ear) of the ear. Subsequently, a group of cells of the ear vesicle becomes detached and gives rise to the acoustic ganglion. Neurons of this ganglion become connected by their nerve fibres to the sensory cells in the labyrinth, on the one hand, and with the brain (the medulla), on the other. The ear vesicle, acting on the surrounding mesenchyme, induces the latter to aggregate around the labyrinth and form the ear capsule. Further parts with various origins are added to the ear: the middle ear, from a pharyngeal pouch and the associated skeleton, and the external ear (where present), from epidermis and dermis.

The olfactory organ

      The olfactory organ develops from a thickening of the epidermis adjacent to the neural fold at the anterior end of the neural plate. This thickening is converted into a pocket or sac but does not lose connection with the exterior. The openings of the sac become the external nares, and the cavity of the sac becomes the nasal cavity. Some cells of the olfactory sac differentiate as sensory epithelium and produce nerve fibres entering the forebrain. In most fishes the olfactory sac does not communicate with the oral cavity; in lungfishes and in terrestrial vertebrates, however, canals develop from the olfactory sacs to the oral cavity, where they open by internal nares. A cartilaginous capsule forms around the olfactory organ from cells believed to have been derived from the walls of the sac itself, and thus it is ectodermal in origin.

Gustatory and other organs

      Gustatory organs in the form of taste buds develop as local differentiations of the lining of the oral cavity but also, in fishes, in the skin epidermis. They are supplied with nerve endings, as are several other sensory bodies scattered among the tissues and organs of the developing body.

The epidermis and its outgrowths

      The major part of the ectodermal epithelium covering the body gives rise to the epidermis of the skin. In fishes and aquatic larvae of amphibians, the many-layered epidermis is provided with unicellular mucous glands. In terrestrial vertebrates, however, the epidermis becomes keratinized; (keratin) i.e., the outer layers of cells produce keratin, a protein that is hardened and is impermeable to water. During the process of keratinization, many cell components degenerate and the cells die; the layer of keratinized cells is therefore shed from time to time. In reptiles (reptile) the shedding may take the form of a molt in which the animal literally crawls out of its own skin. It is less well known that frogs (frog) and toads also molt, shedding the surface keratinized layer of their skin (which is usually eaten by the animal). In birds (bird) and mammals, keratinized cells are shed in pieces that are sloughed off, rather than in extensive layers. In many vertebrates local thickenings of the keratinized layer appear in the form of claws, hooves, nails, and horns.

      The epidermis is only the superficial layer of the skin, which is reinforced by the dermis, a connective tissue layer of a much greater thickness. The cells of the dermis are derived from mesoderm and neural-crest cells. In particular the pigment cells found in the dermis of fishes, amphibians, and reptiles are of neural-crest origin. The pigment in the skin of birds and mammals (and also in hairs and feathers) is also produced by neural-crest cells, but in these animals the pigment cells penetrate into the epidermis or deposit their pigment granules there.

      The structure of the skin is further complicated by the development of hairs (hair) and feathers (feather), on the one hand, and of skin glands, on the other. Hairs and feathers develop from a somewhat similar kind of rudiment. The development starts with a local thickening of the epidermal layer, beneath which a group of mesenchyme cells accumulate. In the case of hairs, the epidermal thickening proliferates downward and forms the root of the hair, from which the shaft then grows outward, emerging on the surface of the skin. In the case of feathers, the epidermal thickening bulges outward to form a hollow fingerlike protrusion with a connective tissue core. Secondarily, the shaft of the feather branches characteristically to produce barbs and barbules. In both cases, however, the final structure—shaft of the hair and shaft barbs and barbules of the feather—consists of keratinized and, thus, dead cells.

      The skin of amphibians and mammals (mammal) (but not of birds and reptiles) is provided with numerous skin glands, which develop as ingrowths from the epidermis. A peculiar type of skin gland is the mammary gland of placental mammals. In the first stage of development, mammary-gland rudiments resemble hair rudiments; they are thickenings of the epidermis, with condensed mesenchyme on their inner surfaces. In some mammals (rabbit, man) two continuous epidermal thickenings called mammary lines stretch along either side of the belly of the embryo. Parts of the line corresponding in number and position to the future glands enlarge while the rest of the thickening disappears. The initial thickenings proliferate inward and produce a system of ramified cords, solid at first but hollowed out later, which become the lactiferous, or milk-bearing, ducts of the gland. Further branching at the tips of the ducts gives rise to smaller ducts and to the secretory end sacs, or alveoli, of the gland.

Mesodermal derivatives

The body muscles and axial skeleton

      The somites, formed in the early stages of development from the upper edges of the mesodermal mantle adjoining the notochord, are complex rudiments that subdivide and give rise to very diverse body structures. The coelomic cavity, present initially, becomes obliterated by the side-to-side flattening of the somites, so that the thinner, outer parietal layer of the somite comes in close contact with its thicker visceral layer. The visceral layer of the somite very early subdivides into two parts. The upper, dorsolateral part called the myotome remains compact, giving rise to the body muscles (muscle). The lower, medioventral part of the somite, called the sclerotome, breaks up into mesenchyme, which contributes to the axial skeleton of the embryo—that is, the vertebral column, ribs, and much of the skull. The parietal layer of the somite, at a later stage, is converted into mesenchyme that, together with components of the neural crest, gives rise to the dermis of the skin and, for this reason, is called the dermatome.

      The cells of the myotome are elongated in a longitudinal direction and become differentiated as muscle fibres. The myotomes, originally situated dorsally, expand on either side, penetrating between the skin on the outside and the lateral plates of the mesoderm on the inside, until they meet midventrally; the whole body is thus enclosed in a layer of developing muscle. As the somites and myotomes are segmented, so are the muscles derived from them. Metamerism, or segmentation, a feature in the embryos of all vertebrates, remains preserved only in the adults of fishes and of terrestrial vertebrates that have elongated bodies (salamanders, snakes); it becomes largely erased in four-footed animals that depend on their limbs for locomotion.

      The mesenchyme derived from the sclerotomes condenses as cartilage around the notochord and the spinal cord. It forms the cartilaginous vertebral column and ribs. In the head region it produces a part of the cartilaginous skull, mainly its posterior and ventral parts; anteriorly the somitic mesenchyme is supplemented by mesenchyme from the neural crest. Cartilaginous capsules of the olfactory organ and the ear fuse with the cartilaginous capsule surrounding the brain; to this complex are also added cartilages associated with the jaws and gill skeleton. Cartilage in the vertebral column and in the skull is replaced later in the bony fishes and in the terrestrial vertebrates by bone. At a still later stage, dermal bones are added, which, while they have no precursors in the cartilaginous skeleton, develop in the adjoining mesenchyme.

The appendages: tail and limbs

      The tail in vertebrates is a prolongation of the body beyond the anus. It develops in early stages from the tail bud, immediately dorsal to the blastopore. Material for the tip of the tail is situated slightly forward from the edge of the blastopore. The elongation of the back of the body is greater than that of the belly; as a result the tip of the tail bud is carried beyond the blastopore and thus beyond the anus, which, in the developed embryo, marks the position of the blastopore. The consequence is that a section of the dorsal surface of the embryo comes to lie on the ventral surface of the tail; i.e., becomes inflected. The tail bud is formed from parts that have already been differentiated to a certain extent; prolongations of the neural tube and of the notochord are involved, and endoderm extends into the tail rudiment as the postanal gut, which, however, soon degenerates. The bud is also encased in ectodermal epidermis. In amphibians the somites of the tail are not derived from the chordamesodermal mantle but from the inflected posterior portion of the neural plate, which loses its nervous nature and becomes subdivided into segments corresponding to the somites of the trunk. In higher vertebrates the cells in the interior of the tail bud have an undifferentiated appearance and form a growth zone, at the expense of which parts of the tail (neural tube, notochord, somites) are extended backward as the tail elongates.

      The paired limbs of vertebrates derive their first rudiments from the upper edge of the lateral plate mesoderm. The parietal layer becomes thickened, and cells escape from the epithelial arrangement and form a mesenchymal mass adjoining the ectodermal epithelium at the surface of the body. The ectodermal epithelium over the mass of mesenchyme likewise becomes thickened. In higher vertebrates, the accumulation of mesodermal cells and the thickening of the epidermis occur along the entire length of the trunk, from neck to anus, but in the middle of the trunk they soon disappear, and only the most anterior and the most posterior sections develop further into the rudiments of the forelimbs and hindlimbs, respectively. In fishes, the rudiments of the pectoral and pelvic fins are more extended anteroposteriorly in earlier than in final stages.

      The mesodermal masses of the limb rudiments proliferate, and, covered with thickened epidermis, form on the surface of the body conical protrusions called the limb buds, which, once formed, possess all the materials necessary for limb development. Limb buds may be transplanted into various positions on the body or on the head and there develop into clearly recognizable limbs, conforming to their origin, whether a forelimb or hindlimb, a wing or a leg in birds. This specificity of the limb is carried by the mesodermal part of the rudiment, but a complex interaction between the mesodermal mesenchyme and the ectodermal epidermis is necessary for the normal development of the limb. In four-limbed vertebrates (tetrapods), the tips of the limb buds become flattened and broadened into hand or foot plates. The edge of the plate is indented, forming the rudiments of the digits. Meanwhile, local areas of the mesodermal mesenchyme in the interior of the limb rudiment condense; these are the rudiments of the various components of the limb skeleton. In fishes, small outgrowths from the myotomes enter the limb rudiment to form the muscles of the fins. In tetrapods, however, the limb muscles develop from the same mass of mesenchyme that gives rise to the skeleton. Thus the muscles of the body and the muscles of the limbs have different origins—the first develop from the myotomes (thus from the somites), and the second develop from the lateral plate mesoderm via the limb buds.

      The nerves supplying the limbs grow into the limb rudiments from the spinal cord and the spinal ganglia. The nerves are guided in some way by the limb rudiments, for, if limb rudiments are displaced by transplantation to an abnormal position, the nerves still find their way and establish normal relationships to the limb muscles. Limb rudiments transplanted to sites very far from their normal positions induce local nerves to enter the limb, thereby making it motile.

Excretory (renal system) organs

      The kidneys (kidney) of vertebrates consist of a mass of tubules that develop from the stalks of somites called nephrotomes. In some primitive vertebrates such as cyclostomes, the nephrotome in each segment gives rise to only one tubule, but, in the great majority of vertebrates, mesenchyme from adjacent nephrotomes fuses into a common mass that differentiates into a number of nephric tubules irrespective of the original segmentation of the mesoderm. Under primitive conditions each tubule opens by a funnel (the nephrostome) into the coelomic cavity; the opposite ends of the tubules fuse to form the collecting ducts of the kidney. A collection of capillaries (the glomerulus) becomes associated with the nephric tubule, forming its filtration apparatus. The glomerulus may be situated in the coelomic cavity opposite the nephrostome or, in all the more advanced animals, intercalated into the nephric tubule, forming with the latter a renal corpuscle of the kidney. In adults of all vertebrates above the amphibians, the nephrostomes disappear (or are never formed), so that the tubule begins with the renal corpuscle. Parts of the kidney in vertebrates can be distinguished as the pronephros (most anteriorly, at the forelimb level), the mesonephros (in the midtrunk region), and the metanephros (in the pelvic region). The three sections of the kidney develop at different stages, starting with the pronephros and ending with the metanephros. In their morphology and mode of development, the anterior parts show more primitive conditions than the posterior ones. The pronephros, developing early in embryo formation, is the functional kidney of fish and amphibian larvae. Its collecting duct opens into the hindmost part of the intestine, called the cloaca, and later also serves as the collecting duct of the mesonephros. In reptiles, birds, and mammals (mammal), the pronephros is nonfunctional, although even in these animals its duct persists as the mesonephric duct. The mesonephros develops later and replaces the pronephros as the functional kidney of adult fishes and amphibians and of the embryos of reptiles, birds, and mammals. The tubules of the mesonephros link up with the duct derived from the pronephros. The pronephric duct in fact stimulates the development of mesonephric tubules, and, in its absence, the mesonephros does not develop at all.

      The metanephros is found only in reptiles, birds, and mammals. It replaces the mesonephros of the early embryonic stages and continues as the functional kidney in the postembryonic and adult life of these animals. The metanephros develops from mesenchyme derived from the nephrotomes of the posterior part of the trunk and lying dorsal to the mesonephric duct. The actual differentiation is initiated by a dorsal outgrowth of the mesonephric duct, called the ureteric bud. The ureteric bud grows in the direction of the mesenchyme and becomes the ureter. Having penetrated the mass of mesenchyme, it starts to branch, producing the collecting tubules of the kidney; the mesenchyme, meanwhile, in response to the influence of the duct and its branches, aggregates to form the excretory tubules of the kidney. The influence of the ureter is indispensable for the development of the metanephric excretory tubules, for, if the ureter fails to develop or, in its outgrowth, stops short of reaching the kidney-producing mesenchyme, no kidney develops.

Circulatory organs

      The rudiment of the heart in vertebrates develops from the ventral edges of the mesodermal mantle in the anterior part of the body, immediately adjoining the pharyngeal region. A group of mesodermal cells breaks away from the ventral edge of the lateral plate, takes a position just underneath the pharyngeal endoderm, and becomes arranged in the form of a thin-walled tube, which will become the endocardium, or lining of the heart. In vertebrates with complete cleavage, the endocardial tube is single and medial from its start. In higher vertebrates with meroblastic cleavage—reptiles, birds, and mammals—the embryo in early stages of development is flattened out on the surface of the yolk sac; therefore, what are morphologically the ventral edges of the mesodermal mantle lie far apart on the perimeter of the blastodisc. As a result of this arrangement, two endocardial tubes are formed, one on either side of the embryo. Subsequently, when the embryo becomes separated from the yolk sac, the two endocardial tubes meet in the midline ventral to the pharynx and fuse, producing a single heart rudiment. After the formation of the endocardium, or the lining of the heart, the coelomic cavity in the lateral plate mesoderm adjoining the heart rudiment expands slightly and envelops the endocardial tube or tubes. The heart muscle layer, or myocardium, develops from the visceral (splanchnic) layer of the lateral plate that is in contact with the endocardial tube; the parietal (somatic) layer of the lateral plate forms the pericardium, or covering of the heart. The portion of the coelom surrounding the heart becomes separated from the rest of the body cavity and develops into the pericardial cavity.

      The endocardial tube branches anteriorly into two tubes, the ventral aortas; (aorta) a similar branching of the endocardial tube posteriorly forms the two vitelline veins, which carry blood from the midgut endoderm or from the yolk sac (when present) to the heart.

      In its earliest development, the heart rudiment shows a degree of dependence on the adjoining endoderm. The whole of the endoderm can be removed in newt embryos in the neural-tube stage. In such endodermless embryos, the heart fails to develop, even though the mesoderm destined to form the heart rudiment is left intact.

      The heart is initially a straight tube stretching in an anteroposterior direction. Rather early in development, however, it becomes twisted in a characteristic way and subdivided into four main parts: the most posterior, the sinus venosus; the atrium, which comes to lie at the anteriorly directed bend of the tube; the ventricle, occupying the apex of the posteroventrally directed inflexion; and, most anteriorly, the conus arteriosus. In the course of development in the more advanced vertebrates, the atrium and ventricle become partially or completely subdivided into right and left halves. In amphibians, only the atrium is separated into two halves, by a partition starting from the posterior end. In reptiles, a partition separates the atria and part of the ventricle. In birds and mammals, the subdivision of the heart is complete, with two atria and two ventricles.

      The complete subdivision of the heart is important for separating the pulmonary (pulmonary circulation), or lung, blood supply from the general body circulation. But, if this separation developed early in the embryo, it would create difficulties, since the lungs of the embryo are not functional; the enrichment of the blood with oxygen occurs instead in the placenta. The partition between the atria in mammalian embryos remains incomplete, so that blood returning from the body and from the placenta enters into the right half of the heart but is shunted (through the interatrial foramen) into the left half of the heart and thence again into general circulation. At birth, however, the interatrial foramen is closed by a membraneous flap, and oxygen-depleted blood from the body enters the right atrium, is channelled into the right ventricle, and thence to the lungs for oxygenating.

      In an adult vertebrate, blood vessels (blood vessel) extend to all parts of the body. It would seem that channels for the supply of blood are provided in proportion to the local demand of the tissues; progressively developing organs or parts with particularly intensified function always receive an increased blood supply. The rudiments of blood vessels are always aggregations of mesenchyme cells. In any blood vessel the endothelial tube is formed first, and the muscular and elastic layers are added later.

      The main blood channels in vertebrates develop in certain favoured situations; namely (1) between the endoderm and lateral plate mesoderm; (2) around the kidneys, especially the pronephros and mesonephros; and (3) in connection with the heart, which is a special case of the first category.

      From the paired forward extensions from the heart, the ventral aortas, loops develop between the pharyngeal clefts. These are the aortic arches, which served originally to supply blood to the gills in aquatic vertebrates. The arches are laid down in all vertebrates, six or more being found in cyclostomes and fishes; six are present in the embryos of tetrapods, but the first two are degenerate. The arches of the third pair develop as the carotid arteries, supplying blood to the head. Those of the fourth pair (and, exceptionally, in urodeles also the fifth) join dorsally to form the dorsal aorta, providing blood to most of the body. These are the systemic arches. The arches of the sixth pair are the pulmonary arches; in embryos they carry blood to the dorsal aorta, as well as to the lungs, but in fully developed amniotes (reptiles, birds, and mammals), they carry blood only to the lungs.

      The paired posterior extensions of the heart of the early embryo are the vitelline veins, whose branches spread out between the lateral plate mesoderm and the endoderm, especially the endoderm of the yolk sac, when present. On their way to the heart, the vitelline veins pass through the liver and break up into a system of small channels—the hepatic sinusoids. Parts of the vitelline veins lying posterior to the liver become the hepatic portal veins, which carry blood from the intestine to the liver; the parts of the vitelline veins anterior to the liver become the hepatic veins, which carry blood from the liver to the sinus venosus in lower vertebrates (anamniotes), but become the anterior section of the postcaval vein in amniotes.

      Whereas the vitelline veins and, later, the hepatic portal vein carry blood from the endodermal parts of the embryo and from the yolk sac to the heart, the blood from the mesodermal and ectodermal parts is returned to the heart through a system of cardinal veins. These latter veins start their development in the form of an irregular sinus around the pronephros, connected by the common cardinal veins (ducts of Cuvier), on either side, to the sinus venosus. Extensions anteriorly and posteriorly give rise to the precardinal and postcardinal veins, respectively. The postcaval vein, present in terrestrial vertebrates, is a late acquisition, both in evolution and in embryogenesis; it is a result of the intercommunication of several venous channels, including the anterior portion of the vitelline veins.

      The first blood cells in vertebrate embryos form in association with the intestinal endoderm on the yolk sac. Groups of mesoderm cells derived from the splanchnic layer of the lateral plate (extra-embryonically in cases in which a yolk sac is present) become so-called blood islands, which are particularly conspicuous on the yolk sac of bird embryos (in the area vasculosa). In bird's eggs, the internal cells of the blood island start producing hemoglobin (gas-carrying component of blood) and become the first red blood cells (erythrocytes) as early as the second day of incubation. The outer cells of the blood islands develop into an endothelial layer and form a network of blood vessels covering part of the surface of the yolk sac. The network acquires a connection to the vitelline veins and vitelline arteries (the latter being branches of the dorsal aorta); thus the blood corpuscles formed in the blood islands can enter the general blood circulation.

      At later stages of embryogenesis, blood-cell formation shifts from the blood islands to the liver and, still later, to the bone marrow.

      The lymphatic system, in a manner similar to the blood vessels, develops by the local aggregation of connective tissue to form lymphatic vessels.

Reproductive organs

      In considering the development of reproductive organs, distinctions must be made between: (1) the origin of sex cells (gametes (gamete)), (2) the origin and differentiation of the sex glands, or gonads (gonad) (ovaries (ovary) and testes (testis)), and (3) the origin and development of the supporting parts of the reproductive system (e.g., genital ducts, copulatory organs).

      The germ (germinal) cells, which eventually give rise to the gametes, are often segregated from the somatic, or body, cells at a very early stage—during cleavage and before the subdivision of the embryo into ectoderm, mesoderm, and endoderm. In the invertebrate nematodes, the very first of these primordial germ cells is identifiable after as few as five divisions of the egg cell. The germ cell retains the large chromosomes present in the fertilized egg; in the somatic cells the chromosomes become fragmented. Subsequently, the single germ cell gives rise, by mitotic divisions, to all the gametes in the gonad.

      In vertebrates, primordial germ cells arise outside the gonads, but they cannot be distinguished in early cleavage stages. In amphibians, cytoplasm at the vegetal pole, rich in ribonucleic acids, becomes incorporated into a number of cells, which, during cleavage and gastrulation, lie among the yolky endoderm cells. Later they migrate into the mesodermal layer and become incorporated into the rudiments of the gonads. In higher vertebrates, primordial germ cells can be recognized in the extra-embryonic endoderm of the yolk sac. In mammals, these cells subsequently migrate into the mesoderm and are located in the gonad rudiments. The mouse embryo, for example, originally has fewer than 100 primary germ cells; during their migration, however, their numbers increase as a result of repeated divisions, to 5,000 or more in the gonads.

      Although the primordial germ cells either may appear before the separation of germinal layers or be found originally in the endoderm, the gonads are invariably of mesodermal origin. In vertebrates, the first trace of gonad development is a thickening of the coelomic lining on either side of the dorsal mesentery and medial to the kidney rudiments. The thickening, elongated anteroposteriorly, is known as the germinal ridge. The ridge protrudes into the coelomic cavity, and the fold of thickened epithelium becomes filled with mesenchyme. At this stage the primordial germ cells invade the rudiments of the gonads and become associated with the somatic cells of the germinal ridge. In the functionally differentiated gonads, only the actual gametes and their predecessors (spermatogonia and oogonia) are derived from the primary germ cells; the supporting cells are somatic cells of local mesodermal origin. In the ovaries, the follicle cells surrounding and nourishing the young egg cells (oocytes) are of somatic origin, as are also the connective tissue and blood vessels of the gonad. In the testes, supporting elements called Sertoli cells are somatic cells, as are the interstitial cells, which are scattered between the sperm-carrying tubules of the testes and believed to be the source of male hormones.

      In the early stages of their development—even while the gonad rudiment is being invaded by primordial germ cells—the female and male gonads are in an indifferent stage. Only later does tissue differentiation of the gonads begin and male or female gonadal development proceed.

      The genital ducts, by which the eggs and sperm are carried away from the gonads, are, in vertebrates, linked with the excretory system. In the male, the seminiferous tubules connect with the nephric tubules of the mesonephros, and the sperm are carried to the exterior by way of the mesonephric duct. In males of lower vertebrates, the mesonephric duct thus serves as a channel both for urine and for sex cells. In amniotes the development of the metanephros as the urine excreting organ has freed the mesonephric duct to carry products associated only with reproduction. In the female, a separate duct, the paramesonephric duct (Müllerian duct), develops beside the mesonephric duct. At its anterior end it utilizes the funnels of the pronephric tubules as its entrance (ostium). The paramesonephric duct develops initially in both female and male embryos. The ducts remain in an indifferent stage longer than the gonads. Eventually the sex hormones produced by the differentiating gonads cause a corresponding differentiation of the ducts. The mesonephric ducts, which become reduced in female embryos, remain in male embryos as ducts for conveying sperm (ductus deferens). The paramesonephric ducts, on the other hand, degenerate in male embryos but become the oviducts in female embryos. In mammals, the terminal portions of the paired oviducts differentiate as two uteri, which, in primates and man, fuse to form a single uterus.

      In all terrestrial vertebrates except the placental mammals, the genital ducts, as well as the ducts of excretory organs, open into the cloaca. In mammals, however, the cloaca becomes subdivided into a dorsal part, which conveys the feces, and a ventral part, which receives excretory and genital products. In male mammals the excretory and genital ducts remain connected, having the urethra as their common outlet; in females the urethra serves only for the passage of urine and the uterus opens separately by means of the vagina. In nearly all vertebrates, the male nephric duct is utilized in some degree for the conduction of sperm.

      Copulatory organs have developed independently in several groups of vertebrates having internal fertilization. The penis in mammals develops from an outgrowth called the genital tubercle, located at the anterior edge of the urinogenital orifice. The tubercle is laid down in a similar way in embryos of both sexes, and the region of the urinogenital orifice remains in an indifferent state even longer than do the genital ducts. In a comparatively late stage of embryonic life the genital tubercle of male embryos encloses the urethral canal and becomes the penis; in female embryos it remains small and becomes the clitoris.

Endodermal derivatives

The alimentary canal

      The alimentary canal is the chief organ developing from endoderm. The way it forms depends on the type of egg cleavage. In eggs with holoblastic (complete) cleavage, after gastrulation the invaginated mass of endoderm lines the archenteron, the cavity of which becomes the alimentary canal, or gut. In eggs with meroblastic (partial) cleavage—and also in mammals (despite their complete cleavage)—the endoderm is produced in the form of a sheet lying flat over the yolk-sac cavity. Subsequently, folds of endoderm and splanchnic mesoderm appear—first anteriorly, then laterally, and lastly posteriorly—and sink, converging ventrally under the embryo and cutting off the future gut cavity from the cavity of the yolk sac. The most anterior and posterior portions of the gut separate, but the middle part remains in open communication with the yolk sac throughout embryonic life, eventually becoming reduced to the yolk stalk, which passes through the umbilical cord.

      The alimentary canal of vertebrates becomes differentiated into the oral cavity, pharynx, esophagus, stomach, and intestine. Whether derived from an archenteron or formed by folding of the endodermal sheet, the canal initially does not possess an opening at its anterior end. This is also the case in some lower chordates and echinoderms, which are grouped together with vertebrates as the Deuterostomia, or animals with secondary mouths (mouth).

      In vertebrates, a mouth forms by a rupture at the anterior end, where the endoderm is in contact with ectoderm. The ectoderm of the future mouth region becomes depressed, forming a mouth invagination, or stomodaeum. The ectodermal and endodermal layers separating the cavity of the stomodaeum from the gut fuse to form the oropharyngeal membrane, which thins and ruptures, providing free passage from the exterior to the gut. Because of its mode of origin, the oral cavity is in part lined by ectoderm and in part by endoderm, the two parts becoming indistinguishable. Before the oropharyngeal membrane ruptures, however, a small pocket forms on the dorsal side of the stomodaeal invagination. This, the rudiment of the anterior lobe of the hypophysis, becomes apposed to the ventral surface of the diencephalon and loses its connection with the mouth cavity.

      The anal (anus) opening in some exceptional cases (urodele amphibians) is derived directly from the blastopore, which persists as a narrow canal after completion of gastrulation. In other vertebrates, however, the anus develops either near the location of the former blastopore or in a corresponding region at the posterior end of the embryo, where the last remnants of mesoderm migrated to the interior. It is thus claimed that the anus in vertebrates is derived, directly or indirectly, from the blastopore. The mode of formation of the opening is somewhat similar to that of the mouth. A slight invagination of the ectoderm occurs, and a cloacal membrane forms, separating the ectodermal invagination from the gut cavity. The membrane ruptures later to provide the anus.

The pharynx and its outgrowths

      The anterior portion of the endodermal gut, lying immediately posterior to the mouth cavity, expands laterally as the pharynx. The lateral pockets of the pharyngeal cavity, called the pharyngeal pouches, perforate the mesodermal layer, reach the ectoderm, and break through to form pharyngeal, or gill, clefts. In fishes and larvae of amphibians, these clefts develop gills and become respiratory organs. Pharyngeal pouches develop in the early embryos of all vertebrates, including the air-breathing terrestrial reptiles (reptile), birds, and mammals. The number of pouches has been reduced in the course of evolution from six or more to four in tetrapods, and the posterior pouches may not actually break through.

      The consistent development of pharyngeal pouches and clefts indicates their importance in vertebrate development. Many parts of the vertebrate body are derived from, or dependent on, the pharyngeal pouches; for example, the aortic arches—the most important blood vessels of a vertebrate—develop between successive pharyngeal pouches. Skeletal visceral arches also occur between consecutive pharyngeal pouches (they do not develop if the pharyngeal pouches are prevented from developing). In adult terrestrial vertebrates, parts of the visceral arches are transformed into the hyoid apparatus, supporting the tongue, the auditory ossicles, and parts of the larynx and trachea. Furthermore, some of the material of the pharyngeal pouches is utilized for the formation of the parathyroid glands and the thymus; the former are indispensable glands of internal secretion, and the latter are a source, in mammals, of cells that produce antibodies. The pharynx also produces the rudiment of the thyroid gland as a ventral outgrowth.

The liver, pancreas, and lungs (lung)

      Three additional important organs develop from the endoderm: the liver, the pancreas, and the lungs. The liver develops as a ventral outgrowth of the endodermal gut just posterior to the section that eventually will become the stomach. Initially, the liver takes the form of a tubular gland, but it soon acquires a close relationship to the blood sinuses and capillaries, forming lobules around blood vessels rather than around glandular ducts. The pancreas develops from three independent rudiments: two ventral ones, formed just posterior to the liver rudiment, and a dorsal one. The ventral and the dorsal rudiments fuse in most vertebrates to form one organ with a complicated system of ducts opening into the duodenum, a portion of the small intestine. The lungs develop from a ventral hollow outgrowth of the gut, which is located just posterior to the pharyngeal region; the outgrowth branches into a right and left trunk that grow posteriorly beside the esophagus and then expand into hollow sacs, in lower terrestrial vertebrates, or into a system of tubes, in birds and mammals.

      The endodermal parts of the alimentary system are, along their entire length, encased by the splanchnic mesoderm of the lateral plates. The coelomic cavities of the right and left sides fuse ventral to the gut but remain separated dorsally by their respective walls, which form the dorsal mesentery—a double membrane by which the gut is suspended from the dorsal side of the body cavity and through which blood vessels and nerves reach the gut. The layer of splanchnic mesoderm next to the endoderm produces the connective tissue and muscular layers of the gut. During development of the glands of the alimentary canal (e.g., pancreas, salivary glands), the mesoderm forms a connective tissue capsule around the branching tubules of the gland. The development of the tubules is dependent on this mesodermal capsule and cannot proceed without it.

Postembryonic development

      After partially developing within the egg membranes or within the maternal body, the newly formed individual emerges. The new animal is then born (ejected from the mother's body) or hatched from the egg. The condition of the new organism at the time of birth or hatching differs in various groups of animals, and even among animals within a particular group. In sea urchins, for example, the embryo emerges soon after fertilization, in the blastula stage. Covered with cilia, the sea-urchin blastula swims in the water and proceeds with gastrulation. frog embryos emerge from the egg membranes when the main organs have already begun to develop, but functional differentiation of the tissues is unfinished; for instance, the components of the eyes and ears are far from complete, the mouth is not yet open, and the gut is filled with yolk-laden cells. Certain birds (called precocial) emerge from the egg covered with downy feathers and can run about soon after hatching, whereas others (altricial) hatch naked, with only rudiments of feathers, and are quite unable to move around. Among mammals (mammal) there is a great range in the degree of development at birth. In marsupials, such as opossums and kangaroos, the young are born incompletely developed and very small; the young are then kept for a long time in the pouch of the mother, all the while firmly attached to the teats and suckling. Many small mammals are helpless at birth. Mice are born naked and blind; puppies and kittens are born covered with fur but with unopened eyes. Newborn human babies have their eyes open but cannot move themselves about for several months. Hoofed mammals, on the other hand, bear young that can stand up and run after their mothers within a few hours of birth.

      In birds (bird) the hard shell is broken by the hatchling's beak, which is provided with a sharp tubercle on its top. A similar “egg tooth” (egg tooth) appears on the tip of the snout of hatchling reptiles. Many arthropods have a preformed line of fragility that allows part of the eggshell to be burst open like a lid, allowing the young to emerge. Birth in mammals is effected through the contraction of smooth muscles of the uterus.

The larval phase and metamorphosis

      The organism emerging from the egg or from the maternal body, apart from being incompletely developed, may have an organization more or less different from that of an adult. In some cases the difference is so great that, without knowing the origin of the eggs or without following the young through their full course of development, it would be impossible to know that the young and the adult are of the same animal species. Such young, called larvae (larva), transform into the adult form by a process of metamorphosis. The term larva also applies to young that resemble the adult form but differ from it in some substantial respect, as in possessing organs not present in the adult or in lacking an important structure (apart from sex glands and associated parts, which tend to develop later in life in most animals). Larvae in different animals have special names given to them, such as the tadpole of frogs, the caterpillar of butterflies, and the fry of fishes.

The larval stage

      The development of the embryo into a larva rather than directly into an organism similar to the adult has various advantages. At the time of emergence from the egg, the new individual is relatively small, and the organization that enables the adult to lead a particular mode of life may not be suitable for a miniature copy of the adult. The larva may have to procure food for itself and, being small, may not be able to feed in the same way as the adult. It also may not be able to use effectively the same defense mechanisms the adult possesses. The larval stage enables an animal to avoid such hazards; it provides a mode of life and corresponding organization better suited to the smaller size of the newly emerged organism. Another advantage is that the larva may be able to exploit an entirely different environment because its organization is very different from that of the adults. A terrestrial adult may have aquatic larvae, a flying adult may have burrowing larvae, and a parasitic adult may have a free-living larva. A third advantage of a larval stage emerges in animals whose adult stages are sessile or restricted in their movements; the larvae can move freely, either of their own accord or on water currents. In this way the larvae of sedentary animals serve for the dispersal of the species. Lastly, the larval stage is of great advantage for certain internal parasites (parasitism), which, once inside a host, cannot transfer to another. New hosts are infected instead by the larval stages. (The usual means of attaining this end is for the parasite to produce enormous quantities of eggs and rely on the passive entry of the eggs into the new host with food. A more efficient way, however, is for a mobile larva to enter the new host actively.)

      A large number of marine invertebrates possess floating larvae that have hairlike projections (cilia) as their means of locomotion. There are three main types of larvae, characteristic of large subdivisions of the animal kingdom.

      The planula larva of coelenterates has an elongated shape and cilia covering its entire surface. The internal organization is simple, hardly beyond differentiation into ectoderm and endoderm in the interior. The larva does not feed but serves only for dispersal.

      The trochophore larva is found in many marine invertebrates. Typically, as in polychaetes (polychaete), it has an alimentary canal with mouth and anus and a ring of ciliated cells arranged anterior to the mouth. It also possesses a sensory organ and rudiments of mesoderm. Cilia around the mouth bring in food—unicellular plants and other small particles. The larva thus not only serves for dispersal but also feeds and grows before it transforms into an adult worm. Other trochophore larvae are found in marine mollusks and in certain marine worms. The larva of echinoderms is similar to the trochophore in possessing a gut and a ciliary band, but the arrangement of the latter is different. The echinoderm larva also feeds and grows as well as serves for dispersal.

      Larvae of very different kinds are found in many arthropods. In crustaceans (crustacean) the larva, called nauplius, does not differ substantially in mode of life or means of locomotion from the adult but has fewer appendages than the adult. A typical crustacean nauplius has three pairs of legs and an unpaired simple eye. Additional pairs of appendages and paired compound eyes appear in the course of a sometimes prolonged development. In insects the larva differs from the adult by the absence of wings but, in addition, may have a different mode of life and different way of feeding. Among chordates the tunicates (tunicate) (sea squirts) deserve attention; the larval form is a free-swimming creature, showing unmistakable relation to vertebrates, but the adult is sedentary, with much reduced nervous and muscular systems. The tadpole of a frog differs from the adult in being totally aquatic, in possessing a tail and gills for respiration, and in having a mouth adapted for feeding on plants. The adult frog is adapted to land life, except for reproductive periods, has no tail and no gills, and is an active predator.

metamorphosis

      Metamorphosis, the transformation of the larva into an adult, is a more or less complicated process depending on the degree of difference between the two forms. The transformation may be gradual, extend over a long period, and involve a number of intermediate stages; alternatively, the transformation may be achieved in one step. In the latter case, especially if the difference between the larva and adult is great, large parts of the body of the larva, including all the specifically larval organs, disintegrate (necrobiotic metamorphosis). At the same time, organs of the adult are built up, sometimes from reserve groups of cells that remain undifferentiated or nonfunctional in the larva. A good illustration of the distinction between gradual and abrupt metamorphosis occurs among the insects. In more primitive insects, such as cockroaches and grasshoppers, metamorphosis is gradual. The larva, often referred to as a nymph, has more or less the same organization as the adult, or imago; it feeds in a similar way but differs from the adults in lacking wings and in having incomplete sex organs. The wings appear in later stages of larval life; they are small at first but increase with each molt, and they attain full size and functional capacity at the last (imaginal) one. The larva of other insects, such as beetles, butterflies, and wasps, is a grub or caterpillar, a wormlike creature not even remotely resembling the adult. The difference in organization is so profound that the transformation cannot be achieved gradually, and an intermediate resting, or pupal (pupa), stage is interposed between the larva and imago. The pupa neither feeds nor moves, as the larval organs inside are destroyed and replaced with organs of the adult, including wings and sex organs. Eventually, when formation of the adult organs is complete, the pupal skin is cast off, and the adult emerges. The destruction of the larval parts may be far reaching and include even the skin and most of the alimentary canal. The tissues of the adult are formed from groups of reserve cells that were present all along in the larva as imaginal disks.

      Necrobiotic metamorphosis is observed in the tunicate larva, in which the tail, including notochord, nerve cord, and muscles, and most of the brain, including eye and statocyst, are destroyed at the same time that the large pharyngeal cavity of the adult develops. A tadpole metamorphosing into an adult frog loses its tail—the cells of which are destroyed and devoured by phagocytic cells—its gills, and its larval mouthparts; concurrently the legs of the adult frog develop progressively, the structure of the mouth and alimentary canal change, and the skin acquires a bony (keratinized) layer and a system of subcutaneous glands.

      The complicated changes taking place during metamorphosis, especially in the case of necrobiotic metamorphosis, must be performed in a coordinated way. So that no changes are made prematurely and no organ systems are left behind in the general transformation, some common signal for the change must be provided. For both insect and amphibian metamorphoses, which have been the most extensively studied, the signal is a hormonal one, sent in the blood to all the cells and tissues of the body.

      Metamorphosis in an insect is complicated by the fact that the rigid cuticle covering its body is very restrictive; new features can appear only after a molt, when the old cuticle is replaced by a newly formed one. Molting in insects is caused by the action of two hormones. In the brain of insects, several groups of neurosecretory cells produce the first hormone. This brain hormone does not itself affect molting but stimulates the prothoracic gland, a loose mass of secretory cells situated in the thorax in close association with tracheal tubes. In response to the stimulation by the brain hormone, the prothoracic gland releases into the blood a second hormone, the molting hormone, or ecdysone. Under the influence of ecdysone, the tissues of the body produce a new cuticle under the old one, after which the old cuticle is shed (the actual molting). The new cuticle embodies any new developmental features that were scheduled to appear. The kind of feature that emerges after a molt is controlled by a third organ of internal secretion, the corpus allatum, secretory tissue situated posterior to the brain, near or around the dorsal aorta and usually appearing as a pair of separate or fused organs. The corpora allata emit the juvenile hormone, which, as long as it circulates in the blood, acts to perpetuate the larval form. As the larva approaches the end of its development, however, the corpora allata stop producing juvenile hormone or reduce its quantity; whereupon, the larva, at the next molt, metamorphoses into an adult. Withdrawal of the juvenile hormone is the immediate cause of metamorphosis, in conjunction with the brain hormone and ecdysone, which are responsible for the shedding of the larval cuticle and for the production of the new cuticle embodying the features of the imago. Metamorphosis through the stage of the pupa is effected by diminishing levels of juvenile hormone, which determine first the transformation of the larva into a pupa and, with further reduction of the juvenile-hormone level, the final step of transformation of the pupa into the adult.

      The metamorphosis of a tadpole into a frog also depends upon two hormones: one initiating the process and the other directly influencing the tissues involved in the change. The first hormone is the thyrotropic hormone, produced by the hypophysis. It has no immediate effect on the tissues of the body but activates the thyroid gland to produce several substances, the most important of which is thyroxine. Thyroxine and other iodine-containing compounds circulate in the blood and cause changes that, in their entirety, constitute the process of metamorphosis. It is remarkable that different tissues react in different ways to the presence of thyroxine. The muscles of the tadpole's tail degenerate, whereas the muscles of the trunk and legs are not affected; in fact, the growth and development of limbs are stimulated as a part of metamorphosis. The effect of the hormone depends on the nature of the reacting cells and tissues—i.e., on their competence—just as the embryonic inductor in the earlier stages of development influences only cells with the competence for a particular kind of reaction.

Direct development

      If an animal after birth or emergence from an egg differs from the adult in comparatively minor details (apart from not having functional sex organs), the development is said to be direct. There is no larval stage and no metamorphosis. Direct development does not mean, however, that no changes occur between birth and adulthood. One very obvious change is the growth of the animal.

      The rate of growth—not absolute increase—is highest in the early stages of postembryonic life; subsequently, growth continues to slow, ceasing completely at the attainment of adulthood. The rate of growth is dependent on many factors, both external (feeding, temperature) and internal. Of the internal factors, the most important are hormones, especially the growth hormone produced by the hypophysis. If the growth hormone is produced in insufficient quantities, the result is dwarfism; if it is produced in excessive quantities, the result is gigantism.

      In the case of direct development, the most important change is the attainment of sexual maturity, which is achieved in several steps and involves the action of several hormones. The gonad rudiments and rudiments of the supporting parts of the reproductive system remain inactive long after birth. At the approach of adulthood, however, two sets of hormones come into action: hypophyseal hormones stimulate the gonads to activity, and gonadal hormones (produced by the gonads) cause the supporting sex organs and other sex characters to become fully developed. To become functional, the gonads must be acted upon by secretions from the hypophysis. In immature females the follicle-stimulating hormone, which alone causes the egg follicles and the oocytes to grow, and the luteinizing hormone stimulate the follicle cells to produce the female sex hormone, estrogen, which effects the development of the uterus, the milk glands, and other characteristics of the female sex. In the male, the same hypophyseal hormones are produced, with the result that the testes start to produce sperm and to secrete the male sex hormone, androgen. It appears that the luteinizing hormone is the more active in the male sex, being able to cause both spermatogenesis and androgen secretion. Androgen, in turn, brings about the development of the penis, the descent of the testicles before birth, the appearance of typical male hair growth, and other secondary sex characteristics.

Maturity and death

      Sexual maturity and the ensuing reproductive activity mark the pinnacle of development and morphogenesis and, for many animals, herald the end of life. The biological goal of the entire process is achieved with the launching of the next generation, and the life cycle that runs from the formation of gametes by one generation to the formation of gametes by the next generation is completed. In many animals the females die after laying their eggs; the males may have died earlier, after pairing. Indeed, some males (spiders, praying mantises) are eaten by the females immediately after copulation.

      The developmental period can only truly be said to end with the termination of an organism, for much activity continues to unfold new developmental sequences, not all of them progressive and favourable, to be sure. Senescence, or a decline in abilities, signals advancing age (aging) in mammals but is not a general occurrence in the animal kingdom. Far more animals continue to function at near-peak capacity well into old age. And even among those species—salmons, eels, many moths—whose members die after a single reproductive act, death is relatively swift and not accompanied by a prolonged period of deterioration.

      In most animals the reproductive potential is not exhausted in a single act of gamete production, but the sexually mature individuals remain alive and reproduce repeatedly. In these cases life may extend long beyond the first attainment of reproductive ability and be accompanied by further growth of the individuals, as occurs in most fishes, amphibians, and reptiles, and also in mollusks and certain other invertebrates. In the case of prolonged life spans, however, reproductive activity may cease with advancing age, and a senile involution take place, as is observed mainly in mammals and, particularly, in man. The changes taking place may be described as regressive development. In most animals, however, the end of life is not preceded by any overt traces of senility. As a general rule, then, the attainment of reproductive ability may be said to be the final phase of progressive development among animals.

      A gradual loss of alertness and vigour is typical of the aging pattern of primates and is especially important to man.

Boris Ivan Balinsky

Additional Reading

General textbooks covering animal development include J. Brachet and H. Alexandre, Introduction to Molecular Embryology, 2nd totally rev. and enlarged ed. (1986); and Gerald M. Edelman, Topobiology: An Introduction to Molecular Embryology (1988). Hans Spemann, Embryonic Development and Induction (1938, reprinted 1988; originally published in German, 1936), is a classic exposition of the experimental method in embryology. Additional useful works are Robert Wall, This Side Up: Spatial Determination in the Early Development of Animals (1990); D.R. Johnson, The Genetics of the Skeleton: Animal Models of Skeletal Development (1986); John Phillip Trinkaus, Cells into Organs: The Forces That Shape the Embryo, 2nd ed. (1984); Elizabeth S. Watts (ed.), Nonhuman Primate Models for Human Growth and Development (1985), which compares both physical and behavioral growth among the primates, including humans; Matthew H. Kaufman, The Atlas of Mouse Development (1992); Claudio D. Stern and Phil W. Ingham (eds.), Gastrulation (1992); Brian K. Hall, The Neural Crest (1988); Brigid Hogan et al., Manipulating the Mouse Embryo: A Laboratory Manual, 2nd ed. (1994); and the work by Wilkins, cited above in the section on animal malformations.

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