The neural crest (NC) originates in the central nervous system (CNS) primordium. Born as an epithelium, NC progenitors undergo an epithelial-to-mesenchymal transition that generates cellular movement away from the CNS. Mesenchymal NC progenitors then migrate through stereotypic pathways characteristic of various axial levels until homing to distinct primordia where phenotypic differentiation takes place. Being the source of most of the peripheral nervous system, pigment cells and ectomesenchyme, the embryonic NC is considered to be a multipotent population of precursors. In spite of numerous recent studies, an essential and still unsolved question is when during ontogeny do the different lineages segregate from putative homogeneous and multipotent progenitors. Evidence suggests that the premigratory NC still resident in the dorsal neural tube epithelium is composed both of multipotent as well as of fate-restricted precursors, supporting the notion of an early appearance of cellular heterogeneity. Understanding these changing states of commitment is a prerequisite for deciphering molecular mechanisms that regulate fate segregation of the embryonic NC. In this review, we present data illustrating the existence of progenitors harboring different states of specification and their emergence as a function of time and space.
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