MASH-1 - A MARKER AND A MUTATION FOR MAMMALIAN NEURAL CREST DEVELOPMENT

The ability to generate mice containing null mutations in any cloned g ene promises new insights into the molecular control of mammalian neur al crest development. This approach has recently been applied to MASH- 1, a transcription factor in the bHLH family that is a mammalian homol ogue of the Drosophila proneural genes achaete-scute. In wild-type emb ryos, this gene is expressed early in the development of the autonomic nervous system, in apparent precursors of sympathetic, parasympatheti c, and enteric neurons (as well as in restricted regions of the centra l nervous system). A null mutation in the MASH-I gene eliminates sympa thetic and parasympathetic neurons and enteric neurons of the foregut (esophagus); however, enteric neurons of the stomach and hindgut are o nly partially affected. Analysis with other markers indicates that the mutation acts after neural crest cells have localized in the anlagen of the autonomic nervous system to prevent neuronal differentiation. T he differentiation of autonomic glia appears unaffected. Thus, MASH-1 provides one of the most specific mutations affecting neural developme nt in mammals, as well as a valuable marker to study the early segrega tion of neural crest cell lineages.