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Piebald lethal (sl) acts early to disrupt the development of neural crest-derived melanocytes
1Department of Molecular Biology, Princeton University, NJ 08544-1014.
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.
Insights
The piebald lethal (sl) mutation in mice disrupts neural crest development, preventing melanocyte precursor cells from reaching hair follicles and causing white coats. This mutation acts early, before key protein expression, affecting melanoblast distribution.
Area of Science:
- Developmental biology
- Genetics
- Cell biology
Background:
- The piebald lethal (sl) mutation in mice results in a white coat phenotype.
- This is due to a lack of neural crest-derived melanocytes in hair follicles.
- Understanding when the sl gene impacts melanocyte lineage is crucial.
Purpose of the Study:
- To determine the timing of the piebald lethal (sl) gene's effect on melanocyte lineage development.
- To compare the distribution of melanocyte precursors in wild-type versus mutant embryos.
Main Methods:
- Used an antibody specific for tyrosinase-related protein 2 (TRP-2) to identify melanocyte precursors.
- Examined TRP-2 positive cell distribution in wild-type and homozygous sl/sl mouse embryos at various developmental stages (10.5–13.5 days postcoitum).
Main Results:
- TRP-2 positive cells appeared in wild-type embryos by 10.5 days, with highest density in head and tail regions by 11.5–13.5 days.
- In sl/sl embryos, TRP-2 staining was limited to non-neural crest-derived melanocytes (retinal epithelium, telencephalon).
- Few TRP-2 positive cells were found in areas normally colonized by neural crest-derived melanocytes in mutant embryos.
Conclusions:
- The piebald lethal mutation disrupts neural crest-derived melanocyte development before TRP-2 expression onset.
- The observed non-uniform distribution of melanoblasts in wild-type mice suggests piebald acts stochastically.