title: Notch1 and Notch2 receptors influence progressive hair graying in a dose-dependent manner.
abstract: The Notch signaling pathway is involved in diverse biological processes such as cell fate decisions or stem cell maintenance. In this study, we assessed the role of this pathway for melanocyte development and hair pigmentation using RBP-Jkappa, Notch1, and Notch2 conditional knockout mice. Disruption of the Notch pathway by inactivating RBP-Jkappa in the melanocyte lineage using Tyr::Cre mice led to a severe coat color dilution. Similarly, hair graying was observed when Notch1 and/or Notch2 receptors were ablated in melanocytes. This phenotype was proportional to the number of floxed Notch alleles, with the most pronounced effect seen in Tyr::Cre/degrees; Notch1(flox/flox); Notch2(flox/flox) mice. Deletion of Notch1 and/or Notch2 in melanoblasts did not induce a congenital defect. The number of Dct-expressing cells at embryonic stages was not affected, but melanocytes located within the hair matrix progressively disappeared during the first regeneration of the hair follicle. In contrast, non-follicular melanocytes and pigmentation in the dermis and in the choroid were not affected. We suggest that both Notch1 and Notch2 receptors contribute to the maintenance of melanoblasts and melanocyte stem cells, and are essential for proper hair pigmentation.
authors.affiliation: ISREC (Swiss Institute for Experimental Cancer Research), National Center of Competence in Research Molecular Oncology, Epalinges, Switzerland.
authors.forename: Karine
authors.initials: K
authors.lastname: Schouwey
authors.forename: Véronique
authors.initials: V
authors.lastname: Delmas
authors.forename: Lionel
authors.initials: L
authors.lastname: Larue
authors.forename: Ursula
authors.initials: U
authors.lastname: Zimber-Strobl
authors.forename: Lothar J
authors.initials: LJ
authors.lastname: Strobl
authors.forename: Freddy
authors.initials: F
authors.lastname: Radtke
authors.forename: Friedrich
authors.initials: F
authors.lastname: Beermann
mesh_terms: D000483:Alleles; D000818:Animals; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000378:metabolism; D005838:Genotype; D006200:Hair Color / Q000502:physiology*; D018859:Hair Follicle / Q000196:embryology / Q000378:metabolism*; D017403:In Situ Hybridization; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051881:Receptor, Notch1; D051883:Receptor, Notch2; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase