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, 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 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. 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, and in the cyclostomes (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, birds, and mammals

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, 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 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, 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, 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. 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; 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, 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 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, the most important gland of internal secretion (i.e., endocrine 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, or nerve cells. They produce outgrowths called axons 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; 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).

Major sense organs

The eye

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

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 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; 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 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 and toads also molt, shedding the surface keratinized layer of their skin (which is usually eaten by the animal). In birds and mammals, keratinized cells are shed in pieces that are sloughed off, rather than in extensive layers. In many vertebrates local