THE ONTOGENY OF THE NEURAL CREST

The neural crest is part of a larger embryonic structure, the neural f olds, belonging to the neural primordium of the Vertebrate embryo. The neural fold is formed by the anterior and lateral ridges of the neura l anlage, which fuse mediodorsally when the neural tube closes. Anteri orly, the epithelium of the neural fold does not convert into mesenchy mal cells and yields Rathke's pouch, the olfactory organ and the epith elium of the mouth roof, of the upper lip and of the frontal region of the head. From the level of the diencephalon (at the level of the epi physis) downwards the neural fold epithelium undergoes the epitheliome senchymal transition and yields the neural crest cells which become la ter on highly diversified and form various structures and tissues thro ughout the body. A large amount of data have shown that the environmen tal cues exerted on crest cells both during their migration and when t hey have reached their target sites are critical in determining their fate. In order to understand the mechanisms through which environmenta l factors influence crest cell differentiation, the developmental capa cities of single neural crest cells were investigated at different tim e points of their ontogeny. Single cell cultures of crest cells have r evealed that already at the migratory stage the neural crest is made u p of cells at different states of determination. In particular, the an alysis of clones obtained from single cell cultures of cephalic migrat ory crest cells has shown that, although many clonogenic cells are mul tipotent to varying degrees, others are committed to give rise to one single derivative. Totipotent progenitors able to generate representat ives of virtually all the phenotypes (neuronal, glial, melanocytic and mesectodermal) encountered in cephalic neural crest derivatives were also found. We proposed that they represent stem cells analogous to th ose which in the hemopoietic system generate the various types of bloo d cells. The neural crest stem cell gives rise to diverse progenitors that become progressively restricted in their potentialities according to an essentially stochastic mechanism while dividing during and afte r completion of die migration process. Similar cloning experiments of crest cells that have already reached their target organs, i. e. senso ry ganglia or enteric plexuses, showed that the phenotypic repertoire expressed by crest-derived cells decreases with increasing embryonic a ge. Efforts are made to elucidate the nature of the factors which infl uence either the survival and/or the differentiation of neural crest c ells in the various types of environments in which they evolve. For ex ample, several proteic growth factors like BDNF, NT3, bFGF were shown to influence the early neural crest derivatives of the peripheral nerv ous system (PNS) while they are in the process of gangliogenesis.