B-Raf and C-Raf Are Required for Melanocyte Stem Cell Self-Maintenance

B-Raf and C-Raf kinases have emerged as criticalplayers in melanoma. However, little is known abouttheir role during development and homeostasisof the melanocyte lineage. Here, we report thatknockout of B-raf and C-raf genes in this lineageresultsinnormal pigmentation at birth with nodefectin migration, proliferation, or differentiation of mela-noblasts in mouse hair follicles. In contrast, thedouble raf knockout mice displayed hair grayingresulting from a defect in cell-cycle entry of melano-cyte stem cells (MSCs) and their subsequent deple-tion in the hair follicle bulge. Therefore, Raf signalingis dispensable for early melanocyte lineage develop-ment, but necessary for MSC maintenance.