B-Raf and C-Raf are required for melanocyte stem cell self-maintenance

Cell Rep. 2012 Oct 25;2(4):774-80. doi: 10.1016/j.celrep.2012.08.020. Epub 2012 Sep 27.


B-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hair Follicle / physiology
  • Melanocytes / cytology*
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins B-raf / deficiency
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Proto-Oncogene Proteins c-raf / deficiency
  • Proto-Oncogene Proteins c-raf / genetics
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Signal Transduction
  • Stem Cell Factor / metabolism
  • Stem Cells / cytology*
  • Xenopus / growth & development


  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-raf
  • Extracellular Signal-Regulated MAP Kinases