MASH genes and the logic of neural crest cell lineage diversification

Avian embryos have traditionally been the system of choice for studying neural crest development, but the combination of reverse genetics and clonal culture should allow new insights to be gained from mammalian systems as well. We describe one of the first examples where a targeted mutation in a developmental control gene, isolated on the basis of its homology to Drosophila neural determination genes, causes a highly selective phenotype affecting the early development of a subset of neural crest derivatives. Detailed analysis of the cellular phenotype and expression pattern of the gene, called MASH-1, have led to novel insights into the genetic logic that controls neural crest development. Most important, some features of the phenotype appear inconsistent with the predictions of current models of neural crest lineage diversification. These unexpected results have forced a reevaluation of our thinking about some aspects of neural crest development, and illustrate the power of the reverse genetic approach to reveal unanticipated features of complex biological systems as well as to suggest new directions for future study.