ECTOPIC C-KIT EXPRESSION AFFECTS THE FATE OF MELANOCYTE PRECURSORS INPATCH MUTANT EMBRYOS

The Patch (Ph) mutation In the mouse, a deletion that includes the gen e for PDGFR alpha, is a recessive lethal that exhibits a dominant pigm ent phenotype in heterozygotes. To assess whether the Ph mutation acts cell-autonomously or nonautonomously on melanocyte development, we ha ve examined the melanogenic potential of neural crest populations from normal and mutant crest cells in vitro and the pattern of dispersal a nd survival of melanocyte precursors (MPs) in vivo. We report that tru nk neural crest cells from homozygous Ph embryos give rise to pigmente d melanocytes in vitro in response to Steel factor (SlF). In vivo, hom ozygous Ph embryos 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 subseq uently disappear. Although dermal mesenchyme is adversely affected in Ph homozygotes, SIF mRNA expression by the cells of the dermatome is n ormal in Ph embryos when neural crest-derived MPs start to migrate on the lateral pathway. In contrast, mRNA for the SlF receptor, c-kit, wa s observed to be ectopically expressed in somites and lateral mesenchy me in embryos carrying the Ph mutation. Based on this ectopic expressi on of c-kit in Ph mutant embryos, and the observed distribution of SLP protein in normal and mutant embryos, we suggest that competition for limited amounts of SIF localized on the lateral neural crest migratio n pathway alters melanocyte dispersal and survival. (C) 1996 Academic Press, Inc.