The ontogeny of the neural crest.

The neural crest is part of a larger embryonic structure, the neural folds, belonging to the neural primordium of the Vertebrate embryo. The neural fold is formed by the anterior and lateral ridges of the neural anlage, which fuse mediodorsally when the neural tube closes. Anteriorly, the epithelium of the neural fold does not convert into mesenchymal cells and yields Rathke's pouch, the olfactory organ and the epithelium 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 epiphysis) downwards the neural fold epithelium undergoes the epitheliomesenchymal transition and yields the neural crest cells which become later on highly diversified and form various structures and tissues throughout the body. A large amount of data have shown that the environmental cues exerted on crest cells both during their migration and when they have reached their target sites are critical in determining their fate. In order to understand the mechanisms through which environmental factors influence crest cell differentiation, the developmental capacities of single neural crest cells were investigated at different time points of their ontogeny. Single cell cultures of crest cells have revealed that already at the migratory stage the neural crest is made up of cells at different states of determination. In particular, the analysis of clones obtained from single cell cultures of cephalic migratory crest cells has shown that, although many clonogenic cells are multipotent to varying degrees, others are committed to give rise to one single derivative. Totipotent progenitors able to generate representatives 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 those which in the hemopoietic system generate the various types of blood 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 after completion of the migration process. Similar cloning experiments of crest cells that have already reached their target organs, i. e. sensory ganglia or enteric plexuses, showed that the phenotypic repertoire expressed by crest-derived cells decreases with increasing embryonic age. Efforts are made to elucidate the nature of the factors which influence either the survival and/or the differentiation of neural crest cells in the various types of environments in which they evolve.(ABSTRACT TRUNCATED AT 400 WORDS)