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

SummaryB-Raf and C-Raf kinases have emerged as critical players in melanoma. However, little is known about their role during development and homeostasis of the melanocyte lineage. Here, we report that knockout of B-raf and C-raf genes in this lineage results in normal pigmentation at birth with no defect in migration, proliferation, or differentiation of melanoblasts in mouse hair follicles. In contrast, the double raf knockout mice displayed hair graying resulting from a defect in cell-cycle entry of melanocyte stem cells (MSCs) and their subsequent depletion in the hair follicle bulge. Therefore, Raf signaling is dispensable for early melanocyte lineage development, but necessary for MSC maintenance.

Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► Direct in vivo evidence of the involvement of Raf proteins in stemness
► B-Raf and C-Raf are required for melanocyte stem cell self-maintenance
► The Raf/MEK/ERK pathway is not essential for melanocyte lineage development
► SCF/Kit and Raf/ERK signaling pathways are uncoupled in the melanocyte lineage