Neural Crest: Origin, Migration and Differentiation

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Abstract The neural crest is a population of cells that emigrates from the dorsal neural tube during early embryogenesis and migrates extensively to give rise to a myriad of cell types. Patterns of migration are controlled largely by extracellular cues in the environment. Neural crest cells are initially multipotent. Cell fate specification – the selection of an individual cell fate from all the possibilities available to a multipotent progenitor – is likely to involve a series of steps, in which cells become progressively restricted to individual fates, a process that is likely to begin while still in the dorsal neural tube, but which then is usually completed during, or even after migration. Extracellular cues in the migratory and postmigratory environment act together with intrinsic transcription factors to ensure that specific fates are chosen. Together, these result in expression of one or more transcription factors that activate or cement a gene regulatory network that establishes and maintains expression of the differentiated phenotype. Key Concepts: The neural crest is an important tissue, as reflected in its nickname, ‘the fourth germ layer’. Neural crest cells give rise to many different cell‐types. Neural crest cells are induced at the boundary of the developing neural plate and prospective epidermis. Neural crest induction depends on BMP signalling in the prospective epidermis and Wnt signalling from the underlying mesoderm. These signals induce neural crest in two phases, specification of the neural plate border, and specification/maintenance of definitive neural crest. Neural crest migration patterns are complex, and usually specific to the derivative fate adopted. Neural crest migration is controlled by the environmental distribution of repellent and attractive/permissive signals, with cell‐type specific receptor expression in the neural crest cells determining their response. While some or all neural crest cells are initially multipotent, specification of individual derivative fates likely results from progressive fate restriction. Neural crest fate specification involves a combination of intracellular and extracellular factors. Fate specification results from transcriptional activation of key genes encoding (a combination of) specific transcription factors. These transcription factors activate and maintain the fate‐specific gene regulatory networks that characterise each cell‐type.