title: B-Raf and C-Raf are required for melanocyte stem cell self-maintenance.
abstract: 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.
authors.affiliation: Institut Curie, Centre Universitaire, Orsay F-91405, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Valluet
authors.forename: Sabine
authors.initials: S
authors.lastname: Druillennec
authors.forename: Céline
authors.initials: C
authors.lastname: Barbotin
authors.forename: Coralie
authors.initials: C
authors.lastname: Dorard
authors.forename: Anne H
authors.initials: AH
authors.lastname: Monsoro-Burq
authors.forename: Magalie
authors.initials: M
authors.lastname: Larcher
authors.forename: Celio
authors.initials: C
authors.lastname: Pouponnot
authors.forename: Manuela
authors.initials: M
authors.lastname: Baccarini
authors.forename: Lionel
authors.initials: L
authors.lastname: Larue
authors.forename: Alain
authors.initials: A
authors.lastname: Eychène
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018859:Hair Follicle / Q000502:physiology; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D048493:Proto-Oncogene Proteins B-raf / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D014981:Xenopus / Q000254:growth & development
chemical_list: D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases