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. 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.

Keywords: neural crest cells; morphogenetic movement; extracellular matrix; fate specification; melanocyte; sensory neuron; pigment cell

Figure 1.

Fate map of the neural crest derivatives in a stage‐14 chicken embryo.

Figure 2.

Sections through the trunk of (a) a neural plate‐stage embryo, (b) a neurulation‐stage embryo and (c) at the completion of neurulation, when the neural crest cells are beginning to migrate. At the neural plate stage, neural crest cells are not yet specified, but under the influence of BMP4/7 (indicated in blue) produced by the ectoderm, neural crest cells (NC) are induced to form from the edges of the neural plate (or neural folds). N, notochord; NC, neural crest cells; NF, neural fold; NP, neural plate; S, somite.

Figure 3.

Sections through the trunk of a chicken embryo showing the early (a), mid (b) and late (c) stages of neural crest migration. Initially, neural crest cells (NC) migrate ventrally between the neural tube and somite (S). Once they reach the somite, they enter at the interface of the myotome (M) and sclerotome (SC), and migrate laterally across the somite. The cells localise near the dorsal aorta to form the sympathetic ganglia (SY), align along the ventral root motor fibres (VR) and differentiate into glial cells, or coalesce near the dorsal neural tube and constitute the sensory or dorsal root ganglia (DRG). Twenty‐four hours after migration has begun, NC begin to invade the dorsolateral path. EC, ectoderm; NC, notochord.

Figure 4.

Comparison of migratory routes, fates and timing between mouse, chicken and zebrafish. Note that iridoblasts and xanthoblasts are the incompletely differentiated precursors for two pigment cell‐types (iridophores and xanthophores) found widely in fish, amphibians and reptiles, but secondarily lost from avian and mammalian lineages. dm, dermomyotome; nt, neural tube. Reproduced by permission of Kelsh et al.. © Elsevier.

Figure 5.

Fate specification in the neural crest. In the direct fate restriction model, multipotent neural crest cells (circles) maintain full multipotency (rainbow fill) during migration; local environmental cues, represented by coloured squares, determine fate selected (unicoloured diverse shapes). Arrows represent time, but also reflect likely cell division. In the progressive fate restriction model, neural crest cells in a premigratory position are initially fully multipotent, but then they undergo a process of progressive restriction of fate potential (represented by decreased colour options in fill), until single fate has been selected. For simplicity, only four distinct cell fates, and two bipotent intermediate progenitors, are shown. Note that environmental influences during or post‐migration are likely to influence the fates specified.

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Further Reading

Betancur P, Bronner‐Fraser M and Sauka‐Spengler T (2010) Assembling neural crest regulatory circuits into a gene regulatory network. Annual Reviews Cellular and Developmental Biology 26: 581–603.

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Pavan WJ and Raible DW (2012) Specification of neural crest into sensory neuron and melanocyte lineages. Developmental Biology 366: 55–63.

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Kelsh, Robert N, and Erickson, Carol A(Mar 2013) Neural Crest: Origin, Migration and Differentiation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000786.pub2]