title: Piebald lethal (sl) acts early to disrupt the development of neural crest-derived melanocytes.
abstract: Mice homozygous for the piebald lethal (sl) mutation have a predominantly white coat due to the absence of neural crest-derived melanocytes in the hair follicles. To investigate the time in embryonic development when the s1 gene affects the melanocyte lineage, we compared the distribution of melanocyte precursors in wild-type and mutant embryos, using an antibody specific for tyrosinase-related protein 2 (TRP-2). TRP-2 positive cells were first observed adjacent to the anterior cardinal vein in 10.5-day postcoitem wild-type embryos. From 11.5 to 13.5 days postcoitem, there was a nonuniform distribution of TRP-2 positive cells along the anterior-posterior axis, with the highest density of cells in the head and tail regions. Along the dorsal-ventral axis, the cells were restricted to positions lateral, but never dorsal, to the neural tube. In homozygous sl/sl embryos TRP-2 staining was restricted to the non-neural crest-derived melanocytes of the pigmented retinal epithelium and the telencephalon. Few positive cells were seen in areas that will form neural crest-derived melanocytes in the inner ear, skin, hair follicles, leg musculature, or heart. We conclude that the piebald lethal mutation acts prior to the onset of TRP-2 expression to disrupt the development of neural crest-derived melanocytes. The non-uniform distribution of melanoblasts in wild-type mice suggests that piebald acts stochastically to affect melanocyte development.
authors.affiliation: Department of Molecular Biology, Princeton University, NJ 08544-1014.
authors.forename: W J
authors.initials: WJ
authors.lastname: Pavan
authors.forename: S M
authors.initials: SM
authors.lastname: Tilghman
mesh_terms: D000818:Animals; D002455:Cell Division; D004622:Embryo, Mammalian; D005804:Genes, Lethal; D006257:Head; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000276:immunology; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology; D016116:Piebaldism / Q000196:embryology / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase