Development of the Neural crest in Xenopus: from induction to cell migration

Lead Research Organisation: University College London
Department Name: Cell and Developmental Biology

Abstract

The neural crest is a migratory cell population found in all vertebrate embryos, that generates several different cell types. In the head, these cells form specific components of the face, while in the trunk they generate the peripheral nervous system, melanocytes, etc.
The mechanisms that control neural crest induction are just beginning to be understood. However, it has not been possible to explain how differences between head and trunk neural crest are generated. It is known that several genes are required for the development of neural crest cells, and that mutations of the human homologues of some of these genes are responsible for certain diseases, such as Hirschprungs and Saethre-Chotzen diseases and Waardenburg-Shah syndrome. However, no analysis has been carried out to explain how, once induced, crest cells are transformed into highly migratory cells or how these genes could be involved in this process.
Here we will use amphibian embryos to investigate the signals that initiate crest production in the head and trunk. We will study the relationship between the genes that are specifically activated in the crest, and how all these factors control the migration of the crest cells, necessary to produce a normal embryo.

Technical Summary

The neural crest is a transient, migratory population of cells, with stem-cell-like properties, found in all vertebrate embryos. It forms at the border of the neural plate, and it is from here that the crest cells migrate to different parts of the embryo where they differentiate into a wide range of cell types. Despite their multipotency, some intrinsic differences exist between neural crest in the trunk and in the head which are set up very early in development.
The identification of genes expressed in the prospective neural crest has allowed important advances to be made in the analysis of crest induction. The expression of specific early markers has led to a general model of neural crest induction. However, several important questions remain unresolved. First, all the molecular markers used to generate the model are initially, or exclusively expressed in the cephalic neural crest only. Second, it is not clear whether the induced cells migrate and differentiate as crest cells. Third, it remains unclear whether different steps of neural crest induction are required to produce all types of crest cells. Finally, many new genes that code for transcription factors and that are expressed specifically in the prospective neural crest have been studied, but the hierarchical relationship between them is unknown. In this project, we propose to address these important questions.
We will use specific molecular markers to distinguish cephalic from trunk neural crest and analyse whether similar mechanisms induce both types of neural crest cells. We will study both early and late phases of neural crest induction. We will examine some of the components of the genetic cascade activated in neural crest cells, e.g. Msx1, Hairy2A, Snail, Slug, Zic5, FoxD3, Twist, Sox9, Sox10. By making use of inducible forms of wild-type and dominant negative constructs of these factors, we will analyse the relationships between them. Finally, we will study the migration of the neural crest in vivo, both in normal embryos and in embryos where molecules involved in cell movement, signalling molecules that induce the neural crest, as well as some of the above-mentioned transcription factors have been modified.
Our aim is to generate a cellular and molecular model that explains how head and trunk crest cells are induced, to understand the genetic cascade governing cell behaviour, and how the induced cells become a highly migratory cell population.

Publications

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