Development and evolution of the migratory neural crest: a gene regulatory perspective

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The neural crest, a uniquely vertebrate characteristic, gives rise to pigment cells, much of the peripheral nervous system, the craniofacial skeleton, and a plethora of other cell types. Classical embryological studies have revealed important details about the migratory pathways followed by these cells, and their subsequent differentiation into diverse derivatives. More recently, many aspects of the molecular cascade of events involved in neural crest induction and generation of these migratory cells have been revealed. Formation of the neural crest appears to involve a network of interactions whereby signaling molecules initiate the induction and, subsequently, the establishment of the neural plate border, which is marked by expression of a characteristic set of transcription factors designated as neural plate border-specifiers. These in turn regulate other transcription factors termed neural crest-specifiers, which control genes involved in neural crest delamination, the generation of migratory cells and ultimately the acquisition of appropriate fates.

Introduction

Neural crest cells initially arise in the central nervous system, at the interface between the neural plate and the adjacent non-neural ectoderm. Prior to emigration from the neural tube, presumptive neural crest progenitors are found in a domain that is located in the dorsal neural tube and which expresses a characteristic suite of transcription factors; notable among these are Snail2 (previously known as Slug) and Sox9. Neural crest cells first become morphologically identifiable as they lose their connections to other neuroepithelial cells, delaminate from the forming neural tube and commence migration to diverse and sometimes distant destinations in the periphery. Thus, a neural crest cell can be defined by a combination of its initial location and the types of molecular markers it expresses, as well as by its subsequent migration and ability to form particular derivatives.

This review focuses on the molecular cascade of events involved in generating this migratory cell population in a variety of vertebrates, with the goal of informing on both its embryonic and evolutionary origin. Using the network representation proposed by Meulemans and Bronner-Fraser [1••] as a framework, we present some of the most recent data that further its elaboration. We address recent findings concerning the role of post-transcriptional regulation in altering the function of neural crest specifier genes and provide an update on signaling pathways that guide neural crest migration. Finally, we discuss the evolutionary origin of the neural crest through changes in the regulatory state that defines it.

Section snippets

Defining gene regulatory modules that function in neural crest formation

Combining data from numerous laboratories working on many different species of vertebrates, the process of generating a migratory neural crest cell and subsequently its wide-ranging derivatives can be hypothetically subdivided into several gene regulatory sub-networks [1••]. First, extracellular signaling molecules (e.g. Wnt, Fgf, Bmp and Notch) emanating from surrounding tissues (e.g. underlying mesoderm and prospective epidermis) are thought to induce a set of genes termed ‘neural plate

Is the neural crest a vertebrate evolutionary novelty?

The neural crest is assumed to be a vertebrate synapomorphy, a derived character unique to this group. The neural crest and ectodermal placodes were considered to be vertebrate innovations, and their invention was intimately linked to the evolution of vertebrates. According to Gans and Northcutt's “New head” theory, the presence of neural crest cells and ectodermal placodes provided the embryological basis for the formation of a set of novel, vertebrate-specific structures, including cranial

Conclusions

Neural crest cells are defined by their regulatory state, position and ability to differentiate into broad derivatives. Further work will refine the nature of the neural crest regulatory network at the transcriptional and post-transcriptional level. In particular, it will be important to define the molecular regulatory sub-networks that bestow stem cell characteristics on the neural crest, enable maintenance of the progenitor state, and account for proliferation and size regulation. Direct

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

We are grateful to Drs Sujata Bhattacharyya, Laura Gammill, Daniel Meulemans and Vivian Lee for advice and critical comments on the manuscript.

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