TitlePiebald lethal (sl) acts early to disrupt the development of neural crest-derived melanocytes.
Publication TypeJournal Article
Year of Publication1994
AuthorsPavan, WJ, Tilghman, SM
JournalProc Natl Acad Sci U S A
Date Published1994 Jul 19
KeywordsAnimals, Cell Division, Embryo, Mammalian, Genes, Lethal, Head, Immunohistochemistry, Intramolecular Oxidoreductases, Isomerases, Melanocytes, Mice, Mice, Inbred C57BL, Mutation, Neural Crest, Piebaldism, Polymerase Chain Reaction

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.