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Induction of the neural crest: a multigene process

Key Points

  • Neural crest cells are a migratory population of cells that originate from the border between the neural plate and the non-neural ectoderm.

  • Induction at the neural plate border is difficult to define; it probably involves many steps and the cells show remarkable plasticity in their cell-fate determination (here, induction of Slug expression is considered to be coincident with the induction of the neural crest).

  • Two models have been proposed for induction of the neural crest: the neural induction model and the two-signal model, both of which involve an interplay between BMP signalling and inhibition, as well as WNT (Wingless-related) and FGF (fibroblast growth factor) signalling.

  • The source of signalling that is required for neural crest induction is still controversial — some experiments indicate that it is the paraxial mesoderm, whereas others indicate that the signals come from the epithelial–neural plate border.

  • Notch signalling, a secreted protein Noelin and zebrafish Narrowminded have also been implicated in neural crest induction.

  • Signals that induce the neural crest turn on the expression of transcription factors such as Slug, Pax, Fox, Zic, Sox and Meis, all of which direct neural crest differentiation.

Abstract

In the embryo, the neural crest is an important population of cells that gives rise to diverse derivatives, including the peripheral nervous system and the craniofacial skeleton. Evolutionarily, the neural crest is of interest as an important innovation in vertebrates. Experimentally, it represents an excellent system for studying fundamental developmental processes, such as tissue induction. Classical embryologists have identified interactions between tissues that lead to neural crest formation. More recently, geneticists and molecular biologists have identified the genes that are involved in these interactions; this recent work has revealed that induction of the neural crest is a complex multistep process that involves many genes.

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Figure 1: Regions that form neural crest during neurulation in a hypothetical vertebrate embryo.
Figure 2: Dynamic expression patterns of Wnts and BMPs in the ectoderm of frog and chick.

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Acknowledgements

The authors thank T. Moreno for help with the figures, and M. García-Castro and M. Albrecht for critical reading of the manuscript.

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Correspondence to Marianne Bronner-Fraser.

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DATABASES

LocusLink

BMP4

BMP7

Foxd3

Pax3

Snail

snailhouse

somitabun

swirl/bmp2b

Wingless

Wnt1

Wnt3a

WNT3A

FURTHER INFORMATION

Encyclopedia of Life Sciences

Neural crest: origin, migration and differentiation

Vertebrate embryo: patterning the neural crest lineage

Glossary

NEURAL TUBE

A cylindrical structure that runs through the midline of the embryo; it expands in the head to form the brain and in the trunk to form the spinal cord.

NEURAL FOLDS

Tips of invaginating ectoderm that will close to form the dorsal portion of the neural tube.

PLACODES

Thickenings in the vertebrate cranial ectoderm that invaginate and form parts of cranial sensory ganglia and paired sensory organs.

AUTONOMIC NEURONS

Nerve cells of the peripheral nervous system that innervate the viscera, smooth muscles and exocrine glands.

PHARYNGEAL DENTICLES

Dense structures on the surface of pharyngeal arches of early vertebrates that are thought to be pressure sensitive.

GASTRULATION

Morphogenetic movement that transforms a single-layered embryo into an embryo with three germ layers.

HAMBURGER–HAMILTON STAGES

Stages that describe the age of chick embryos; stage 2 refers to the time before gastrulation.

EPIBLAST

A term for the embryonic layer in chicks, mice and humans from which the embryo proper arises during gastrulation.

MORPHOLINO ANTISENSE OLIGONUCLEOTIDES

Modified antisense oligonucleotides that are designed to block translation by pairing with the translation start site in the 5′ untranslated region.

PARAXIAL MESODERM

Mesoderm that is adjacent to the neural tube and that is destined to form somites.

SOMITES

Mesodermal balls of cells adjacent to the neural tube that will differentiate into the muscle, vertebrae and dermis.

ROHON–BEARD SENSORY NEURONS

Early-differentiating neurons in the dorsal neural tube of fish and amphibians.

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Knecht, A., Bronner-Fraser, M. Induction of the neural crest: a multigene process. Nat Rev Genet 3, 453–461 (2002). https://doi.org/10.1038/nrg819

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