Stem cells and transcription factors in the development of the mammalian neural crest

Abstract

The neural crest is a migratory population of multipotent embryonic cells that generates the neurons and glia of the peripheral nervous system, as well as a variety of non-neural mesectodermal and endocrine cell types. The study of neural crest cell and molecular biology provides a system to investigate how such multipotent cells choose their fates, and whether the repertoire of fates becomes progressively restricted with time. The study of mammalian neural crest development has lagged behind studies of avian crest development due to the relative inaccessibility of mammalian embryos. The development of reverse genetic methods in mice, however, has made the analysis of mammalian neural crest development both more attractive and more tractable. Rodent neural crest cells have been isolated and grown in clonogenic cultures, where they behave as multipotent stem cells. This system provides an assay for factors that influence the differentiation of these multipotent cells. Transcription factors provide valuable early markers for neural crest cells as well as molecular handles on the lineage segregation process. One such factor is Mash1, a homolog of the Drosophila proneural genes, achaete-scute. Mash1 marks autonomic progenitor cells and is essential for their development in vivo, as shown by gene knockout experiments.