Ectopic c-kit Expression Affects the Fate of Melanocyte Precursors inPatchMutant Embryos

AbstractThePatch(Ph) mutation in the mouse, a deletion that includes the gene for PDGFRα, is a recessive lethal that exhibits a dominant pigment phenotype in heterozygotes. To assess whether thePhmutation acts cell-autonomously or non-autonomously on melanocyte development, we have examined the melanogenic potential of neural crest populations from normal and mutant crest cellsin vitroand the pattern of dispersal and survival of melanocyte precursors (MPs)in vivo.We report that trunk neural crest cells from homozygousPhembryos give rise to pigmented melanocytesin vitroin response to Steel factor (SlF).In vivo,homozygousPhembryos contain a subpopulation of crest-derived cells that express c-kit and tyrosinase-related protein-2 characteristic of MPs. These cells begin to migrate normally on the lateral crest migration pathway, but then fail to disperse in the dermal mesenchyme and subsequently disappear. Although dermal mesenchyme is adversely affected inPhhomozygotes, SlF mRNA expression by the cells of the dermatome is normal inPhembryos when neural crest-derived MPs start to migrate on the lateral pathway. In contrast, mRNA for the SlF receptor, c-kit, was observed to be ectopically expressed in somites and lateral mesenchyme in embryos carrying thePhmutation. Based on this ectopic expression of c-kit inPhmutant embryos, and the observed distribution of SlF protein in normal and mutant embryos, we suggest that competition for limited amounts of SlF localized on the lateral neural crest migration pathway alters melanocyte dispersal and survival