Cells in focus
Neural crest cells: a model for invasive behavior

https://doi.org/10.1016/S1357-2725(03)00243-7Get rights and content

Abstract

Neural crest cells are the embryonic precursors of the neurons and glia of the peripheral nervous system, pigment cells, and connective tissue in the face, neck and heart. They are induced near the junction of the neural plate and embryonic ectoderm and undergo an epithelial to mesenchymal transition (EMT). Neural crest cells then display invasive behavior and migrate into the surrounding tissues along specific pathways. Neural crest cells are amenable to study in tissue culture, and the molecules that regulate their development can be studied in vivo with antisense techniques as well as with the expression of gain and loss-of-function constructs. Mutations in factors that regulate neural crest cell survival or differentiation can lead to cell death or the premature cessation of their migration, resulting in craniofacial abnormalities, pigmentation defects and the absence of enteric neurons. This paper reviews recent advances in our understanding of neural crest cell induction and migration, emphasizing both avian and amphibian models.
Cell facts

  • The embryonic progenitors of pigment cells, the neurons and glia of the peripheral nervous system, as well as connective tissue in the face, neck and heart.

  • Induced to form at the boundary of the neuroepithelium and embryonic ectoderm.

  • Expression of the transcription factors Snail, Slug and FoxD3 leads to delamination from the neural tube.

  • Invasive motility not unlike that of tumor cells can be studied in vitro.

  • Express proteases, distinctive cell surface receptors and glycoproteins to acquire an invasive phenotype.

  • Mutations of transcription factors expressed by the neural crest or in other factors that inhibit their premature differentiation can lead to survival and migration-associated birth defects.

Introduction

It has been argued that the key difference between a vertebrate and an invertebrate is not a vertebral column, but the presence of migrating neural crest cells in the embryos of the former but not the latter. Neural crest cells from fish to primates first appear in an epithelial to mesenchymal transition (EMT) from the margins of the neural plate or from the dorsal-most neural tube shortly after neurulation is complete (Fig. 1). From this humble beginning neural crest cells go on to accomplish great things. In avian embryos, a model system commonly used by biologists who study the neural crest, neural crest cells become highly migratory and invade the surrounding tissues in waves. In the trunk, neural crest cells first migrate ventrally into the narrow space between the somites and neural tube. Then they turn ventrolaterally into the somites themselves, restricting their migration to the rostral sclerotome and avoiding inhibitory cues in the caudal half of the somite (see a review of barrier molecules by Krull, 2001). A second wave of migration then takes neural crest cells into the space between the somites and the overlying embryonic ectoderm. Neural crest cells in the first, ventrally migrating wave differentiate into adrenal chromaffin cells and the neurons and glia of the peripheral nervous system, while the neural crest cells that move dorsolaterally differentiate into pigment cells. In the head, neural crest cells not only become neurons, glia and pigment cells, but also differentiate into connective tissue in the jaw, oral cavity, conotruncus, neck and orbit (reviewed by LeDouarin & Kalcheim, 1999). Here, I will describe the molecules that have been identified as regulators of neural crest cell induction, both the history and recent advances in our understanding of the molecular basis underlying neural crest cell motility, and our current understanding of representative birth defects resulting from abnormal neural crest cell morphogenesis.

Section snippets

Cell origin and plasticity

Why do some cells leave the neuroepithelium as neural crest cells? The neurula of the amphibian Xenopus laevis, which is amenable to early surgical and genetic manipulation, has been widely used for these experiments (reviewed by Wu, Saint-Jeannet, & Klein, 2003). At least in Xenopus neural crest cells are induced at the boundary between the neural plate and the embryonic ectoderm near the midpoint in a gradient of bone morphogenetic protein (BMP) expression: BMP expression in the neural plate

Functions

Neural crest cells have evolved as a way of moving a subset of neuroepithelial cells out into surrounding tissues where they differentiate into appropriate cell types. Therefore, it may seem obvious that neural crest cells must be motile. In fact, the migratory behavior of fibroblasts derived from neural crest cells was studied in detail decades ago in isolated avian corneas (Bard & Hay, 1975). However, a series of papers in the mid-1980s reported that latex beads microinjected near the chick

Associated pathologies

The abnormal proliferation, survival, migration or differentiation of neural crest cells can lead to one or more congenital defects. Some of the more common defects attributed to abnormal neural crest cell morphogenesis include craniofacial abnormalities, albinism and insufficient development of the peripheral nervous system. Experimental organisms like Xenopus and the mouse have been used to identify or confirm the roles of mutated genes suspected to generate these abnormalities. For example,

Acknowledgements

The author would like to thank A. Paulson and C.A. Erickson for their careful reading of the manuscript, as well as R. Harris, W. Halfter and D. Liverani for providing micrographs of neural crest cells in vitro.

References (20)

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