SOLUBLE AND CELL-BOUND FORMS OF STEEL FACTOR ACTIVITY PLAY DISTINCT ROLES IN MELANOCYTE PRECURSOR DISPERSAL AND SURVIVAL ON THE LATERAL NEURAL CREST MIGRATION PATHWAY

Trunk neural crest cells segregate from the neuroepithelium and enter a 'migration staging area' lateral to the embryonic neural tube, After some crest cells in the migration staging area have begun to migrate on a medial pathway, a subpopulation of crest-derived cells remaining in the migration staging area expresses mRNAs for the receptor tyrosin e kinase, c-kit, and tyrosinase-related protein-2, both of which are c haracteristic of melanocyte precursors. These putative melanocyte prec ursors are subsequently observed on the lateral crest migration pathwa y between the dermatome and overlying epithelium, and then dispersed i n nascent dermal mesenchyme. Melanocyte precursors transiently require the c-kit ligand, Steel factor for survival. Although Steel factor mR NA is transiently expressed in the dorsal dermatome before the onset o f trunk neural crest cell dispersal on the lateral pathway, it is no l onger produced by dermatomal cells when melanocyte precursors have dis persed in the dermal mesenchyme. To assess the role of Steel factor in migration of melanocyte precursors on the lateral pathway, we analyze d melanocyte precursor dispersal and fate on the lateral pathway of tw o different Sl mutants, Sl, a null allele, and Sl(d), which lacks cell surface-associated Steel factor but produces a soluble form. No melan ocyte precursors were detected in the dermatome of embryos homozygous for the Sl allele or in W mutants that lack functional c-kit. In contr ast, in embryos homozygous for the Sl(d) allele, melanocyte precursors appeared on the lateral pathway, but subsequently disappear from the dermis. These results suggest that soluble Steel factor is required fo r melanocyte precursor dispersal on the lateral pathway, or for their initial survival in the migration staging area. In contrast, membrane- bound Steel factor appears to promote melanocyte precursor survival in the dermis.