Molecular analysis of neural crest formation

doi:10.1016/S0928-4257(01)00074-2

Journal of Physiology-Paris

Volume 96, Issues 1–2, January–March 2002, Pages 3-8

https://doi.org/10.1016/S0928-4257(01)00074-2 Get rights and content

Abstract

Neural crest cells arise within the ectoderm during neurulation and give rise to most of the peripheral nervous system. Following neural tube closure, they come to lie within the dorsal neural tube from which they emerge and subsequently migrate extensively to numerous and characteristic sites. There, they differentiate into neurons and glia of the peripheral nervous system, cartilage and bone of the face, melanocytes and various other cell types. Fate mapping experiments have demonstrated that the neural crest arises at the juncture between presumptive epidermis and neural plate. However, injection of lineage tracer into individual cells reveals that single neural fold cells are not committed to a neural crest fate; rather these cells can form all ectodermal derivatives (epidermis, neural tube, neural crest). Inductive interactions between the neural and non-neural ectoderm can generate neural crest cells, suggesting that signals travel through the epidermis to generate neural crest cells prior to neural tube closure. Induction of the neural crest appears to be a multiphasic process and involves a combination of an early Wnt signal together with later functions of BMP signaling pathways. We have used a variety of molecular screens to isolate molecular constituents involved in neural crest formation. We have identified a secreted factor, Noelin-1, which is expressed in the prospective avian neural plate and may play a role making the neural tube competent to form neural crest. Noelin-1 mRNA is expressed in a graded pattern in the closing neural tube, with highest expression in the neural folds and no detectable expression at the ventral midline. Its expression precedes that of Slug, a zinc finger transcription factor that represents the earliest known neural crest marker gene. Over-expression of Noelin-1 using recombinant retroviruses causes an excess of neural crest emigration and prolongs the time that the neural tube is competent to generate and regenerate neural crest cells. These results support an important role for Noelin-1 in rendering the neural tube competent to respond to inductive cues to generate neural crest.

Introduction

The vertebrate nervous system primarily arises from the neural plate, with the remaining contribution coming from the sensory epidermal placodes. During neurulation, the neural plate thickens and invaginates to form the neural tube. Presumptive neural crest cells lie at the border region between the neural plate and non-neural ectoderm, coming to occupy the dorsal portion of the neuroepithelium after neural tube closure (Fig. 1). At the time of neurulation, a divergence has been thought to occur between the central and peripheral nervous systems. While the former arises from the neural tube proper, the latter derives from neural crest cells at the junction of the neural plate and the lateral ectoderm.

Following neural tube closure, neural crest cells lie within the dorsal portion of the neural tube and begin to emigrate shortly thereafter (Fig. 1). Initiation of neural crest cell migration proceeds in a head-to-tailward (rostrocaudal) wave. After emigration, these cells move in a highly patterned fashion through neighboring tissues. They localize in diverse but characteristic sites within the embryo and give rise to many diverse derivatives, including sensory and sympathetic ganglia, melanocytes and cartilage of the face.

Section snippets

Cell lineage analysis of neural tube and neural folds

Shortly after neural tube closure, all neuroepithelial cells appear morphologically similar. Those destined to form neural crest cells reside within the dorsal portion of the neural tube. When individual precursors within the dorsal neural tube or migrating along neural crest pathways are labeled with a lineage tracer, they contribute to form multiple neural crest derivatives as diverse as sensory and sympathetic ganglion cells [3], [4], [6]. In addition to neural crest derivatives, they also

Induction of the neural crest

Throughout neurulation, prospective neural crest cells are located at the boundary between neural plate/neural tube and epidermis. Therefore, one possibility is that interactions between these two cell populations are responsible for the formation of neural crest. Indeed, experiments in amphibian embryos [9] indicate that neural crest cells are generated wherever these tissues approximate. To test whether neural plate-epidermal interactions lead to the formation of neural crest cells in the

Role of BMP signaling in neural crest formation

Bone morphogenetic proteins (BMP) are members of the TGF-β family of secreted signaling molecules. BMP4 and BMP7 have been shown to be sufficient to substitute for the non-neural ectoderm in inducing neural crest cells [8], making BMPs a good candidate for the inducer within the ectoderm. An important question is whether BMPs are necessary for neural crest formation. Careful analysis of the expression patterns of BMP-4 and -7 demonstrate that they are highly dynamic. Although they are expressed

Role of Moelin-1 in rendering the neural tube competent to form neural crest

Our previous cell lineage analyses suggest that the neural crest is not a pre-segregated population of cells within the neural tube; instead, a single progenitor in the dorsal neural tube can contribute to the neural tube (presumptive central nervous system) and neural crest [4]. Furthermore, we have found that neural crest induction and formation occur in the open neural plate and are largely completed by the time of neural tube closure. Because many marker genes that are expressed in the

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Journal of Physiology-Paris

Abstract

Introduction

Section snippets

Cell lineage analysis of neural tube and neural folds

Induction of the neural crest

Role of BMP signaling in neural crest formation

Role of Moelin-1 in rendering the neural tube competent to form neural crest

References (11)

Developmental potential of avian trunk neural crest cells in situ

Neuron

Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm

Cell

The origins of neural crest cells in the axolotl

Dev. Biol.

Noelin-1 is a secreted glycoprotein involved in generation of neural crest

Nature Cell Biology

Timing and competence of neural crest formation

Develop. Neurosci

Cited by (30)

Sox2: To crest or not to crest?

(+)-Cholesten-3-one induces differentiation of neural stem cells into dopaminergic neurons through BMP signaling

Regulation of the noradrenaline neurotransmitter phenotype by the transcription factor AP-2β

SVZa neural stem cells differentiate into distinct lineages in response to BMP4

Development of the peripheral sympathetic nervous system in zebrafish

Neural Cell Specification during Development