The neural crest at the time of its formation is represented by a mass of loose cells lying dorsal to the neural tube. Almost at once after the formation of the crest, the cells of which it consists start migrating in a lateral and ventral direction from the place of their origin.

As the neural crest cells move, they form streams, bypassing, as they go, certain organs (viz., the eye, and the gill pouches). These streams of neural crest cells are especially conspicuous in the head and neck region, while in the trunk region the neural crest cells are more scattered right from the start.

Some of the neural crest cells move into the space between the epidermis and the layer of mesoderm; others penetrate into the interstices between the neural tube and the inner surface of the somites and down to the dorsal aorta and beyond. In their movements the neural crest cells follow mesenchyme-filled spaces between organ rudiments.

Sooner or later, the most advanced neural crest cells reach the mid-ventral line of the body. Not all of them, however, travel as far as this –  rather they become spread all along the path, some of the cells even retaining their original position dorsal to the neural tube.


The migration of the neural crest cells is a complicated process, dependent on many factors. If the neural crest cells are cultivated in vitro, the cells spread evenly in the available medium. In the organism, however, the even distribu­tion of neural crest cells is disturbed by the surrounding tissues and organ rudiments which lie in the path of the migrating cells and are bypassed.

Other rudiments seem to attract the neural crest cells, in some way, or to keep them fixed once they have reached a certain position. Thus, the neural crest cells are held along the upper edges of the somites and also along the upper edge of the lateral plate. Later, when part of the neural crest cells differentiate into chromatophores, these accumulations of neural crest cells become conspicuous as longitudinal strips of pigment.

The migration of neural crest cells can be observed in several different ways. The neural crest cells, being ectodermal cells, are, in amphibians, distinguishable from the mesodermal cells by their smaller content of yolk granules and by a greater amount of pigment derived from the egg. Another way of tracing the neural crest cells in amphib­ians is by means of local vital staining.

If the stain is applied to the neural folds, the neural crest cells derived from these can readily be seen against the background of unstained ectoderm and mesoderm. In birds, migration of neural crest cells has also been traced by using grafts labeled with radioactive substances. Another method is based on the ability of the neural crest cells to differentiate into melanophores.


By isolating parts of the embryo in sufficiently early stages and cultivat­ing them in suitable surroundings, it is possible to prove that without the neural crest cells no pigmentation can develop in the skin or in other organs and tissues. If, however, part of the embryo is isolated and transplanted after the migrating neural crest cells have reached this part, the pigment cells later differentiate in the graft.

The actual differentia­tion of pigment cells occurs after the migration has been completed. While on the move the neural crest cells do not differ in their pigment content from other cells, and this of course makes it difficult to observe their migration directly. This last method of investigat­ing the migrations of neural crest cells has been applied in mammals and birds.

In fishes and amphibians, the pigment cells are found predominantly in the connective tissue—in that of the skin, but also in the peritoneum, in the walls of blood vessels, and elsewhere, In birds and mammals, the pigment is found predominantly in the epidermal derivatives – the hairs and the feathers. Nevertheless, the production of the pigment is also due to the activity of the neural crest cells.

They penetrate into the hair and feather follicles and deposit the pigment granules in the hairs and the feathers as they grow out of the follicles. If the access of the neural crest cells to the hair and feather follicles is precluded, the hairs and feathers may develop normally, but they are completely devoid of pigment.


Besides the pigment cells, other types of cells are also differentiated from the neural crest cells. The visceral skeleton is almost completely developed from neural crest cells. The visceral arches occupy approximately the same position as the streams of neural crest cells in the early embryo.

The mass of neural crest cells behind the eye, that is, between the eye and the first branchial pouch, becomes the mandibular arch, the upper part of which becomes differentiated as the quadrate, and the lower part of which gives rise to the Meckel’s cartilage or the mandible proper.

The mass of neural crest cells between the first and second branchial pouches becomes the hyoid arch; the next mass becomes the first branchial arch, and so forth. The mass of neural crest cells moving downward in front of the eye contributes to the formation of the anterior half of the trabeculae of the skull.

The neural crest cells of the trunk region, on the other hand, do not participate in the development of skeletal tissues, both the axial skeleton (vertebral column) and the limb skeleton being derived from the mesoderm. Rather peculiarly, one element of the visceral skeleton in the amphibians, the second basibranchial, is also of mesodermal origin.

The papillae of the teeth in urodele amphibians have been shown to be derived from neural crest cells. It is highly probable that the papillae of the teeth in all other vertebrates are of the same origin.

The role of the neural crest cells in the development of the peripheral nervous system has been a matter of controversy. At present, it is accepted that the spinal ganglia and the ganglia of the autonomic nervous system are derived from the neural crest cells but that the ganglia of the cranial nerves (V, VII, IX, X) are developed only in part from neural crest, the other part being contributed by the dorsolateral or epibranchial placodes.

In addition to the ganglion cells, the neural crest participates in the development of the nervous system by contributing material for the sheaths of the nerves (Schwann cells) and the meninges (at least the pia mater and arachnoidea). Lastly, the neural crest cells are found to differentiate as subcutaneous connective tissue, although in this case they are joined by mesenchymal cells derived from the mesoderm.

As the neural crest cells may take such divergent paths of differentiation, the question arises as to whether the fate of individual crest cells is determined by environ­mental influences or whether these cells already differ at the time when they leave the neural folds.

Apparently, both the alternatives are partially true. If different parts of the neural fold are explanted in a culture medium or transplanted to the side of an embryo, different results are obtained, depending on the area from which the neural fold has been taken.


Pieces of cranial neural folds under these conditions produce only small numbers of melanophores, but they give rise to cells which may develop into cartilage. Neural folds of the trunk region, when explanted or transplanted, give rise to numerous melanophores, but no pre-cartilage cells are formed.

On the other hand, it has been shown that cartilages develop from neural crest cells only when they are induced to do so by adjoining tissues. Pieces of cranial neural crest were cultivated in an epithelial vesicle either alone or together with other tissues, such as neural plate, notochord, foregut endoderm, mid-gut endoderm, and lateral mesoderm.

Under these conditions, cartilage developed from neural crest cells only when they were cultivated together with foregut endoderm. Trunk neural crest under the same condition produced only melanophores and mesenchyme and no cartilage.

It follows that:

i. Only cranial neural crest is competent to produce cartilage.

ii. It can produce cartilage only under the influence of foregut endoderm. 

It has been noticed further that spinal ganglia are formed only in the immediate vicinity of the neural tube. It would appear that some influence of the tube is necessary for the crest cells to become differentiated in this way. In the sympathet­ic ganglia, however, crest cells acquire neuron differentiation at a distance from the neural tube.

There is some evidence that among the pigment cells in amphib­ians the two types, melanophores and guanophores, are already distinct while the cells are migrating from the site of their origin, the neural folds.