Neural Crest: Origin, Migration and Differentiation

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, but the mechanism whereby cells choose and become committed to individual fates remains a longstanding source of contention. Cell fate specification – the selection of an individual cell fate from all the possibilities available to a multipotent progenitor – is generally considered to be a progressive process. However, a recent flurry of single‐cell transcriptional profiling studies indicates a more dynamic process in which cells with retained multipotency display expression of competing genetic modules specifying different fates. Extracellular cues in the migratory and postmigratory environment act together with intrinsic transcription factors to ensure that specific fates are chosen. 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 specific receptor expression in the neural crest cells determining their response. All neural crest cells are initially multipotent, with specification of individual derivative fates resulting from competition between genetic modules controlling pairs of fates. Nevertheless, it is proposed that these specified cells retain a cryptic full multipotency, most visible in adult neural crest‐derived stem cells. Neural crest fate specification is then a dynamic process in which extracellular factors influence the transcriptional state of the cell, eventually driving it towards a specific fate choice. Fate specification results from transcriptional activation of key genes encoding (a combination of) specific transcription factors. These transcription factors, together with ongoing extracellular signals, activate and maintain the fate‐specific gene regulatory networks that characterise each cell type.