Central Nervous System of Vertebrates | Embryology

In this article we will discuss about:- 1. Introduction to the Development of Central Nervous System 2. Later Development of the Spinal Cord 3. Dependence in Development of Nerves and Nerve Centers on Peripheral Organs 4. Development of the Autonomic Nervous System.   

Introduction to the Development of Central Nervous System:

The central nervous system of vertebrates develops from the primary rudiment, the neural tube. The tube when formed is of unequal diameter throughout; its anterior end is expanded, the cavity is broader, and the walls are thicker than in the posterior part of the tube. These differences foreshadow the development of the brain from the anterior part of the neural tube and the development of the spinal cord from the posterior part.

The various parts of the brain (forebrain, midbrain, etc.) are first indicated as thickenings of the wall of the neural tube, which are followed, especially in the case of the cerebral hemispheres, by the development of pocket-like evaginations of the brain wall. Shallow constrictions develop early all around the neural tube, thus permitting the distinguishing of several “brain vesicles.”

Three such brain vesicles appear at the beginning. The most anterior brain vesicle, the prosencephalon, later gives rise to the telencephalon and the diencephalon. The second brain vesicle, the mesencephalon, is not subdivided further and develops into the midbrain. The third brain vesicle, the rhombencephalon, gives rise to the metencephalon (cerebellum) and the myelencephalon (medulla oblongata).

The medulla oblongata becomes constricted by shallow furrows into a number of segments, neuromeres. This segmentation, which is especially clear in fish embryos, is, however, only temporary and does not leave any trace in the organization of the adult brain. It is not correlated with the metameric arrangements of the cranial nerve.

Even before the prosencephalon is clearly subdivided into the telencephalon and the diencephalon, a pair of saclike protrusions appears on its lateral walls. These protrusions are the rudiments of the eyes which are thus, basically, specially differ­entiated parts of the brain. In this stage, they are called optic vesicles.

The optic vesicles become constricted from the remainder of the prosencephalon, and the connecting optic stalk later forms the basis for the development of the optic nerve. The optic stalk (and the optic nerve) joins that part of the brain vesicle which becomes the diencephalon.

By the method of local vital staining, as well as by observation of peculiarities of pigmentation, it has been possible to trace back the cells of the optic vesicle to the open neural plate. In the neural plate the presumptive material of the optic vesicles lies far forward, close behind the transverse neural fold and rather near to the midline.

In the course of development, the eye rudiments are drawn out away from each other and into a more lateral position than they occupied initially. After the neural tube has been closed, it undergoes considerable stretching, to­gether with the stretching of the embryo as a whole, especially in its posterior half. As this stretching is at the expense of the thickness of the tube, it tends to enhance the difference in bulk between the brain and the spinal cord.

A most peculiar transformation occurs in the posterior part of the neural plate and tube. Here the neural plate reaches the blastopore. The posterior part of the neural tube elongates to a greater extent than the ventral part of the embryo and the posterior end of the neural tube is therefore carried beyond the blastopore.

Because its hindmost tip is attached to the blastopore, the neural tube becomes bent on itself some distance from the blastopore. The apex of the bend then becomes the tip of the tail rudiment. The major part of the neural tube, from its cranial end to the apex of the bend, differentiates as central nervous system (brain and spinal cord).

The inflected part of the tube, however, the part lying between the apex of the tail rudiment and the blastopore, differentiates as muscle of the tail region. It loses its central canal and becomes split along the midline into two lateral masses or strips of cells which forthwith shift upward, so as to lie on both sides of the notochord and spinal cord.

Cranially these cell masses join up with the dorsal part of the mesodermal mantle. Together with the latter, the presumptive muscle of the tail region is subdivided into muscle segments, the somites. No stalks of somites and no lateral plate are developed in the tail region, and in this respect the segmentation of the presumptive muscle derived from the neural plate differs from the segmentation of the trunk mesoderm.

By local vital staining it is possible to determine exactly which part of the neural plate differentiates as caudal muscle and which part differentiates as neural tissue. The boundary between the two parts runs straight across the neural plate at about one sixth the distances to its posterior end.

The roof of the archenteron is responsible for the differentiation of the various parts of the neural plate and neural tube. The anterior part of the archenteron roof— namely, the prechordal plate—induces predominantly the forebrain and eyes (archencephalic inductor), a more posterior part of the archenteron roof induces the hindbrain and associated structures (deuterencephalic inductor), and the most posterior part of the archenteron roof induces spinal cord and muscle (spinocaudal inductor). The induction of muscle by the spinocaudal inductor becomes comprehensible from what has just been stated about the fate of the posterior end of the neural plate.

A corollary to the experiments on the regional specificity of inductors is provided by the following experiments designed to test the determination of parts of the neural plate. It was desired to test whether in the neural plate, after it has already made its appearance but before it starts to differentiate into its subordinate organ rudiments, the various parts are interchangeable or whether they are already determined for their respective destination.

For this purpose pieces of the young neural plate were cut out and reimplanted into the same or another embryo. The transplanted parts were placed in abnormal orienta­tions, as for instance with reversed anterior and posterior ends, or they were placed in an altogether different region of the neural plate.

The result was found to be different depending on whether the pieces of the neural plate were taken with or without the underlying archenteron roof. If the graft consisted of neural plate cells only, it differ­entiated in agreement with its surroundings and the graft’s original polarity, or its place of origin did not manifest itself. Rotated grafts gave rise to parts of the brain which were in complete harmony with their surroundings.

Pieces of neural plate taken from its posterior region and transplanted into the anterior region differ­entiated as brain parts instead of differentiating as spinal cord or muscle. In short, the development of the neural system went on as if nothing had happened. The various parts of the neural plate were found not to be determined, or else their determination was not final and could be overridden by the influence of the surrounding tissues.

If, however, the neural plate material was taken together with the underlying archenteron roof, the graft differentiated in accord with its original prospective significance. Inverted sections of the brain developed if the graft was inverted. The normal location and differentiation of the eyes were disar­ranged if the rotation of a piece involved the eye region of the neural plate.

That this result is due to the rotation of the archenteron roof together with a portion of the neural plate is clearly proved by experiments in which only a piece of archenteron roof was rotated, while the neural plate remained in its normal position.

This experiment caused a derangement in the development of the eyes. The removal of a part of the archenteron roof underlying the eye region of the neural plate causes defects in the development of the brain and eyes; parts of the forebrain are found to be missing, and the eyes are fused into one cyclopic eye.

What has been said in respect to determination of the structure of parts developing from the neural plate (of which the eyes are the most easily recognizable) may be extended to the determination of the functional mechanism developing in the brain.

The normal movements of the forelimb in salamander larvae depend on a central mechanism (“action system” ), which is located in the spinal cord at the level of the three pairs of spinal nerves III, IV, and V which supply the forelimbs.

If the area of the neural plate giving rise to this segment of the spinal cord is excised and replaced by a more posterior part of the neural plate, the graft will fit into its new position and acquire the functional properties necessary for controlling the movements of the forelimbs.

If a similar transplantation is carried out later, in the tail-bud stage, so that the spinal cord at the forelimb level is replaced by a more posterior section of the cord, the graft can no longer fully take over the function of the more anterior section, and the movements of the forelimbs supplied by nerves from the graft are abnormal.

At the same stage (tail-bud), however, the section of the neural tube which develops into the medulla (the rhombencephalon) may be cut out and replaced, with inversion of its anteroposterior axis, and not only does the graft develop into a morphologically perfect medulla, tapering from the anterior end back­ward, but also it acquires a functional polarization in harmony with the rest of the central nervous system. All the nervous responses of the operated larvae, in particular the control of the swimming movements, may be perfectly normal.

These experiments proved that the detailed structure of the central nervous system, on which its functional properties depend, is not determined at the time when the rudiment of the nervous system is first formed, but that the peculiarities of the various parts of the brain and spinal cord are elaborated gradually throughout an extended period.

Further development of the brain and spinal cord is more or less complicated, depending on the degree of perfection that the central nervous system attains in any group of animals.

Whereas in the lower vertebrates, such as elasmobranch fishes and amphibians, the adult conditions do not depart greatly, as far as the shape of the brain is concerned, from the conditions in the embryo, in higher vertebrates (and especially in mammals) the brain, which in the early embryo does not differ greatly from the brain of an amphibian or fish embryo, changes later in a most striking way as a result of progressive development of certain parts.

Later Development of the Spinal Cord:

The spinal cord in later embryonic stages is a tube with the lumen, the central canal, in the form of a vertical slit (as seen in cross section). The lumen is lined by a layer of epithelial cells, the ependyma. At the top and at the bottom of the slit-like central canal, the ependyma forms a roof plate and a floor plate. Laterally the ependyma participates in the proliferation of spinal cord cells which give rise to the mass of nerve cells and neuroglia cells of the cord.

The walls of the spinal cord are thickened laterally, and as the proliferation of cells continues in the sides of the cord, the growth of the lateral parts soon exceeds the growth of the dorsal and ventral walls. Ventrally the tissue of the cord grows downward, leaving in the middle a narrow slit, the ventral median fissure.

Dorsally the central canal becomes compressed; the ependymal layers of the right and left sides fuse and form a membrane-like structure, the dorsal median septum, which separates the masses of nervous tissue above the central canal just as the ventral median fissure separates the nervous tissue beneath the central canal.

Even before the dorsal part of the central canal becomes obliterated, owing to the fusion of the ependymal layers of both sides, a longitudinal, outwardly directed groove appears on the sides of the canal. The groove bears the name of “limiting groove,” and it serves as a margin dividing each lateral wall of the spinal cord into two parts –  the upper part is the dorsolateral plate, and the lower part is the ventrolateral plate.

When the nervous centers of the spinal cord become differentiated, the sensory centers develop in the dorsolateral plate, while the motor centers develop in the ventrolateral plate. In this way, the limiting groove indicates the sub-division of the spinal cord into a sensory region and a motor region. After the obliteration of its dorsal part, the central canal becomes approximately rounded or oval in cross section.

While the gross changes in the shape of the spinal cord and its central canal are pro­ceeding, the cells in the walls of the cord undergo a number of transformations leading eventually to the development of the spinal cord as a functioning part of the nervous system. When the neural tube is first formed, its walls consist of a single layer of pseudostratified neural epithelium.

All cells of this epithelium reach the inner surface of the tube (the tube lumen), but the nuclei of the cells are arranged at different distances from the lumen, giving the impression of several horizons of cells. All cells are anchored at the inner surface of the tube by intercellular connections in the form of desmosomes.

All neuroepithelial cells at this stage are capable of growth and proliferation and are equivalent to one another in this respect. This has been proved by supplying the cells with radioactive thymidine. It was found that over a period of 8 to 10 hours all cells of the neuroepithelium take up thymidine—a clear sign that each cell is preparing for a mitotic division.

When any cell approaches mitosis, however, it rounds off and in so doing is drawn toward the lumen of the tube, where it is connected by desmosomes to other cells at that level. Consequently, all mitoses from late prophase to telophase are seen to occur only next to the lumen of the neural tube.

After mitosis is completed, the two daughter cells elongate again and become indistinguishable from other cells of the neuroepithelium. In this way proliferation of the neuroepithelial cells increases the number of cells in the neural tube and also increases the volume of the tube as a whole.

At a later stage some of the cells of the neuroepithelium start losing their attachment to other cells at the inner surface of the neural tube and slip outward, eventually emerging from the pseudostratified neuroepithelium. This migration outward is ac­companied by the differentiation of these cells into neurons.

While some of the cells start migrating before showing signs of differentiation, it seems to be more common for the cells to start differentiating even before leaving the neuroepithelium. The attenuated outer end of the columnar neuroepithelial cell becomes the neurite and develops a system of neurofibrils, which can be stained by the silver nitrate method. The inner end of the cell also develops neurofibrils and has been recognized as a “transient dendrite.” The cell thus becomes distinctly bipolar.

The cells migrating out of the neuroepithelium accumulate just underneath of what will become the white matter of the spinal cord to form a loose layer of cells called the mantle. In addition to the primary outward migration, nerve cells may undertake more complicated migrations up or down the length of the neural tube, forming concen­trations of nerve cells known to anatomists as the various nuclei of the brain and spinal cord. In the mantle the neurons attain their full functional differentiation.

The “transient dendrite” becomes reduced, so that temporarily the future neurons become unipolar, but soon new, definitive dendrites are formed. After the production of the neurons a further migration of cells from the neuroepithelium gives rise to the astrocytes, the cells of the neuroglia which never acquire nervous functions. The residual neuroepithelium becomes the ependyma.

A considerable number of cells in various parts of the central nervous system degenerate during the embryonic period (during the fifth to sixth days of incubation in the chick), thus enhancing the differences in cell numbers in the various areas. At present, there is no means of finding out in advance what will be the fate of any given cell, but the experiments show that the fates of individual cells are probably not firmly fixed in early stages.

The part of the spinal cord from the central canal to the outer boundary of the mantle contains numerous cells (neurons and neuroglia cells) and is the gray matter of the cord. Outside the mantle lies the margined layer of the cord.

This layer is made up of the processes of the ependymal and neuroglia cells to which the axons of the neurons are later added in increasing numbers. When these become myelinated, the marginal layer acquires a whitish appearance in the fresh state. Hence, this part of the spinal cord is known as the white matter.

Development of Spinal Nerves and Spinal Ganglia:

The spinal cord becomes connected with the organs of the body, the limbs, and the tail by means of spinal nerves. In the development of the spinal nerves a very important part is played by the spinal ganglia. The ganglia do not form from parts of the neural tube but from cells of the neural crest.

Some cells of the neural crest migrate from their site of origin above the neural tube to the sides of the spinal cord and aggregate as small compact masses of cells segmentally arranged along the whole length of the spinal cord. The groups of cells become the rudiments of the spinal ganglia.

Most cells in the spinal ganglia differentiate as nerve cells, and long processes grow out from these cells, connecting them to the peripheral organs and to the spinal cord. The longer processes growing outward mainly to the skin are afferent and sensory and serve to bring nerve impulses to the spinal ganglia and through them to the central nervous system.

The shorter processes growing out toward the spinal cord enter it as the main part of the dorsal roots of the spinal nerves and make connections with the cells in the dorsal columns of the spinal cord. The ventral roots of the spinal nerves are formed by outgrowths of the motor neurons situated in the ventral columns of the spinal cord and are efferent in nature, serving to supply nerve impulses to the somatic muscles of the body. The fibers of the motor nerves are actually the first to be formed.

When the sensory nerves start developing, the outward-growing fibers emerging from the spinal ganglia meet the nerve fibers leaving the spinal cord by way of the ventral roots, and together they form mixed sensory-motor nerves. The nerves branch again to supply different areas of the body.

A dorsal ramus supplies the dorsal integument and muscles of the back. A ventral ramus supplies the side of the body and the ventral surface and also gives off a connecting branch, the ramus communicans, to the ganglia of the autonomic nervous system.

The limbs of vertebrates are supplied by the spinal nerves belonging to several segments in the case of both fore- and hind-limbs. Before entering the limbs, the nerves become interconnected, forming plexuses – the brachial plexus for the forelimb and the lumbar plexus for the hind-limb.

Dependence in Development of Nerves and Nerve Centers on Peripheral Organs:

It is common knowledge that the nerves and nerve centers show a certain correspondence in the degree of their development with the organs they supply. Thus, the spinal nerves supplying the limbs in terrestrial animals are stronger than the other spinal nerves, the corresponding ganglia are larger, and the spinal cord itself has swellings in the cervical and the lumbar regions, from which the fore- and hind-limbs are innervated.

It can be shown experimentally that, at least in part, this correspondence in the degree of development of the nervous system and the peripheral organs are due to a direct correlation between the two. If the forelimb rudiment of a salamander embryo is removed and the limb fails to develop, the nerves of the brachial plexus remain smaller (thinner) than they would have been if the limb were there.

Also, the spinal ganglia III to V are smaller. The number of cells in each ganglion may be reduced to 50 per cent as compared with the normal or the un-operated side of the same animal. If an additional limb rudiment is transplanted, the local spinal nerves supply the nerves to the trans­planted limbs, and then these nerves increase in thickness and the corresponding ganglia increase in size.

The increase in the number of cells may be up to 40 per cent. In similar experiments performed on the chick embryo, the sensory and motor parts of the spinal cord can be shown to be similarly reduced in the absence of a limb and increased in cases of peripheral overloading (transplantation of an additional limb-bud). Reduction occurs in both the gray matter (the cells) and the white matter (the fibers) of the spinal cord.

The mechanism by which the size of the nerve center (a spinal ganglion or a part of the brain or spinal cord) is altered by a change in the periphery is fairly complicated.

When the periphery connected to a nerve center is increased, the increase of nerve cells in the center may be brought about by:

1. Increased proliferation—this has been found in some cases, but seems to be of minor importance.

2. Increase in the number of cells which differentiate as neurons.

3. Decrease in the number of degenerating cells.

All three of these factors may act simultaneously or may become prominent in changing proportions in various cases. The main effect of a decrease in the periphery seems to be a degeneration of large numbers of nerve cells, sometimes as many as 90 per cent in restricted areas having no other peripheral connections. One of the most remarkable facts in this dependence of the nerve centers of the periphery is that cells may apparently be affected although they have no direct connections with peripheral organs.

Nerve cells may degenerate even though the organs to which they should have been related are removed before nervous connection between the central nervous system and the periphery is established. In the case of overloading, cells which do not normally send their processes into the area concerned are drawn into supplying the additional periphery.

Not only the volume (thickness) of the nerves is dependent on the organs which they supply but also the paths which the nerves take, and thus the whole configuration of the peripheral nervous system is determined by the periphery.

The mode of development of the nerves was a subject of controversy as long as embryology relied on purely descriptive methods. The conflicting theories were those of His and Hensen. According to His, the nerves consist of processes growing out from the nerve cells and eventually reach their organs of destination or make contacts with the processes of other nerve cells in the central nervous system.

According to Hensen, the nerve fibers develop from intercellular bridges connecting all the cells of the multicellular animal from the earliest stages of development. The controversy was solved by Harrison (1908), when he tried cultivating in a plasma clot pieces of neural tube taken from frog embryos.

He observed directly the formation of outgrowths from the nerve cells and saw the free ends of the processes push forward through the medium. Harrison’s findings were corroborated by numerous investigators, and it was also shown that the processes of nerve cells can establish new connections in vitro, if nervous tissue is cultivated together with a different type of tissue (e.g., muscle tissue).

The question now arises as to what directs the nerve fibers in their outgrowth from the central nervous system or from the cranial and spinal ganglia to the peripheral organ. The answer is given by the results of embryonic transplantations. If the forelimb rudiment of an amphibian embryo, prior to the outgrowth of the nerves, is cut out and transplanted to a position very near the original one, the brachial nerves will deviate from their normal paths and will be deflected in the direction of the transplanted limb.

If the distance of the transplanted limb from the original position is not too great, the brachial nerves will penetrate into the limb and ramify in it just as if the limb were in its normal position. The limb in this case becomes fully functional and moves in coordina­tion with the other limb.

The same may happen if an additional limb is transplanted into the immediate vicinity of the host limb. The brachial nerves will develop branches running out to the additional limb and will supply it. If the normal path of the nerves is blocked by some obstacle, the outgrowing nerves may avoid the obstacle, go around it, and still reach their normal destination.

This action has been observed when a piece of mica was inserted into a frog embryo between the spinal cord and the region where the hind-limb rudiments were to develop. The nerves formed loops around the mica plate and still reached the hind-limb rudiments.

However, if the limb rudiment is placed farther away from the normal limb site, or if the obstacle between the spinal cord and the limb rudiment is too great, the nerves fail to be attracted to the limb. If the limb rudiment is placed on the side of the embryo, too far for the normal forelimb or hind-limb nerves to reach it, it will still attract the local spinal nerves. These nerves will grow into the limb, but they cannot provide for the normal functioning of the limb – the limb cannot move.

Only the areas of the spinal cord from which the nerves of the brachial and lumbar plexuses originate appear to possess the properties necessary for controlling the func­tion of limbs. These properties, are established at some time between the neurula and the tail-bud stages. The centers controlling the movements of the fore- and hind-limbs are interchangeable, however –  when forelimb buds were transplanted in place of hind-limb rudiments, they acquired normal mobility.

Limbs transplanted to the head may be supplied by fibers of the cranial nerves, and in that case the limbs can be seen to move synchronously with the respiratory movements of the jaws and gills. The movements of the limb are, however, rather of the nature of twitching’s and differ from the coordinated movements of normal limbs.

The last experiment shows that the attraction of the nerves by the peripheral organs may be unspecific to a certain extent, the nerves growing out to organs other than the ones they normally supply. This conclusion is further borne out by the following experiment. An eye was transplanted into the side of a salamander embryo after the forelimb rudiment was removed. The brachial nerves were deflected from their normal path and grew out toward the transplanted eye.

Having approached the eye, however, the brachial nerves failed to penetrate into the eye and to establish an actual connection with it but stopped with free ends in the tissue surrounding the eye. Two aspects of the nerve supply to organs must thus be recognized – one aspect is the outgrowth of nerves toward the organ, and the other aspect is the actual establishment of a connection between the nerve and the organ.

The attraction of the outgrowing nerves to peripheral organs seems to be unspecific to a very high degree; possibly any growing mass of tissue will attract a nerve that is sufficiently near to it. The connections between the nerve and the end organ, however, can be made only if the two correspond to each other, at least in a general way.

It has been shown that the interaction between the nervous system and the periphery is at least in part dependent on a chemical substance called the nerve growth factor, which is secreted by some tissues of the body. The nerve growth factor was discovered when a piece of a malignant tumor (mouse sarcoma 180) was transplanted into a chick embryo. It was found that nerve fibers grew in abundance and penetrated the transplanted tumor tissue, and also that the sympathetic ganglia of the host embryo were greatly increased in size.

In subsequent work carried out by Dr. Levi-Montalcini and her associates it was found that the nerve growth factor was produced not only by the tumor used in the original experiments, but also by other tissues. It is produced in great quantities by the mouse sub-maxillary salivary gland; it is contained in snake venom (the snake venom glands are specially modified salivary glands!); and it is also produced in minute quantities in a number of other tissues.

Using the sources which contain the substance in mass, a chemical purification and analysis of the nerve growth factor was undertaken, and it was found to be a protein consisting of two conjugated identical molecules, each consisting of 118 amino-acid residues. The action of the nerve growth factor is most easily tested on sympathetic ganglia grown in tissue culture.

In the absence of the factor there is little activity in the explanted ganglion. With nerve growth factor added, however, the ganglionic cells produce a copious outgrowth of nerve fibers. Injection of the substance into newborn mice causes a great increase in the size of the sympathetic ganglia—up to 12-fold—and proliferation of the sympathetic nerve fibers much greater than normal.

Deprivation of the nerve growth factor has the opposite effect. This can be achieved by preparing an antibody to the purified nerve growth factor, and injecting it into newborn mice. The result is that the sympathetic ganglia are reduced to insignificant vestiges, with corresponding reduction of sympathetic innerva­tion.

Apart from the generalized effect discussed above, the nerve growth factor also has a local effect – it appears to direct the outgrowth of sympathetic nerve fibers toward the source from which the substance is diffusing. In one experiment attempting to prove this, a sympathetic ganglion was cultivated in a chamber connected by very narrow channels to two other chambers, only one of which contained the nerve growth factor.

The nerve fibers from the ganglion grew out toward and into the chamber containing the nerve growth factor, but not into the chamber devoid of the factor. As it is found that some normal tissues of the embryo produce the nerve growth factor, it can be concluded that the outgrowth of the nerve fibers toward these tissues is caused by the substance.

It also has been found that the nerve growth factor may have a direct effect on the assembly, in the cytoplasm of nerve cells, of microtubules and microfilaments, which are instrumental in the formation and maintenance of nerve cell outgrowths.

The increase or decrease in the size of sympathetic ganglia is in part due to the changes in size of individual nerve cells, but the effect is mainly on the number of cells of the ganglion rudiment which actually differentiate as nerve cells, and on the number of cells which degenerate—the mechanism.

It appears that the nerve growth factor, as investigated in the experiments, is specific for the sympathetic nervous system. Whether the somatic and parasympathetic nervous systems are under the control of a substance of a similar nature has not so far been proved.

A counterpart to the dependence of the nervous system on the peripheral organs is the influence that the nerves exercise on the organs which they supply. This influence does not concern the initial stages in the development of organs but is sometimes very important for their subsequent differentiation.

The muscles are originally formed before the nerves are developed, and the differentiation of muscle tissue may proceed for some time in the complete absence of nerve supply, such as when the entire neural plate is removed in an early stage of development.

The histological differentiation may proceed so far that the muscles become functional; that is, they may show contractions, spon­taneously or as reactions to direct stimulation. If the innervation of the muscle does not occur, however, the muscle fibers undergo a fatty degeneration and are eventually resorbed. Thus, some sort of trophic influence of the nerves is necessary for the persistence of muscle tissue.

Some sense organs depend for their persistence on the continued influence of the nerve endings supplying them. The gustatory organs in fishes and in man degenerate if the nerve which supplies them (the glossopharyngeal nerve) is interrupted. If a regen­eration of the nerves takes place, the regenerating fibers upon reaching the epithelium cause the epithelial cells to differentiate as gustatory buds in place of the ones that previously degenerated.

Development of the Autonomic Nervous System:

The autonomic nervous system consists exclusively of efferent neurons conveying nervous impulses to the cardiac and smooth muscles, to digestive and sweat glands, and to some endocrine glands.

The bodies of the neurons of the somatic motor nerves and visceral motor nerves are located in the ventrolateral plates of the spinal cord and brain, and the axons of these neurons lead directly to the effector muscles. In the sympathetic system, the pathway from the spinal cord to the effector organ is made up of at least two neurons.

The body of the first neuron lies in the spinal cord, in the lateral part of the ventrolateral plate. The axons leave the spinal cord in the ventral motor roots and then, by way of the rami communicantes, reach a system of sympathetic ganglia lying in two rows to the right and left of the dorsal aorta, where these fibers terminate.

Because the neurons whose bodies are located in the central nervous system reach only as far as the ganglia, they are known as preganglionic neurons. Nerve cells located in sympathetic ganglia, receiving impulses from the preganglionic neurons, forward them to the effector organs directly or by means of further neurons situated in the secondary and even tertiary sympathetic ganglia, the latter being located in the immediate vicinity of the effector organs (on the gut, the bladder, and so forth).

The origin of the preganglionic neurons of the sympathetic system, as well as of the cranial components of the parasympathetic system (visceral efferent components of nerves VII, IX, and X), presents no special problems. The origin of the ganglia of the autonomic system, on the other hand, in particular the origin of the chain of sympathetic ganglia, has been a subject of much controversy. At least three possible sources of these nerve cells have been considered—namely, the neural crest, the neural tube, and the local mesoderm.

After much inconclusive work in which descriptive methods was used, a satisfac­tory solution to the problem has been reached by the use of experimental methods,. When parts of the neural crest are removed in young embryos (of the chick), there is an immediate effect on the development of the sympathetic ganglia, which either are reduced or in some cases may be completely lacking.

The other two sources under consideration (the neural tube and the local mesoderm) were not tampered with in these experiments, so that the defects are clearly an indication that the sympathetic ganglia and the neurons contained in them are of neural crest origin. Even the tertiary sym­pathetic ganglia in the walls of the gut are of neural crest origin and are absent when access of the neural crest cells to the gut rudiment is precluded by operation.

In a separate investigation with the same methods, the ciliary ganglion (the parasympathetic ganglion connected to the oculomotor nerve) also was found to be formed from cells of the neural crest originating in the mesencephalon area of the neural tube.

The actual formation of the sympathetic ganglia takes place in rather early stages of the development of the embryo, before the spinal nerves start growing out. When the neural crest cells migrate downward from their site of origin, dorsal to the neural tube, groups of the migrating cells accumulate along the dorsal aorta.

The cells first aggregate into paired ganglia, and these become linked with one another lengthwise to form a longitudinal nerve cord on each side of the dorsal aorta. The cord is secondarily extended forward into the head region. When the spinal nerves start growing out, they eventually establish connection with the sympathetic trunks by means of the rami communicants.