1. Notch1 and Notch2 receptors influence progressive hair graying in a dose-dependent manner
- Author
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Friedrich Beermann, Véronique Delmas, Freddy Radtke, Lothar J. Strobl, Ursula Zimber-Strobl, Lionel Larue, and Karine Schouwey
- Subjects
endocrine system ,medicine.medical_specialty ,Genotype ,Notch signaling pathway ,Mice, Transgenic ,Melanocyte ,Cell fate determination ,Biology ,Mice ,Dermis ,Internal medicine ,Conditional gene knockout ,medicine ,Animals ,Cell Lineage ,Receptor, Notch2 ,Receptor, Notch1 ,Hair Color ,Alleles ,In Situ Hybridization ,Mice, Knockout ,Embryo, Mammalian ,Hair follicle ,Embryonic stem cell ,Cell biology ,Intramolecular Oxidoreductases ,Phenotype ,medicine.anatomical_structure ,Endocrinology ,melanocyte ,notch ,pigmentation ,coat colory ,transgenic ,hair graying ,stem cell ,Melanocytes ,sense organs ,Stem cell ,Hair Follicle ,Signal Transduction ,Developmental Biology - 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-J kappa, Notch1, and Notch2 conditional knockout mice. Disruption of the Notch pathway by inactivating RBP-J kappa 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.
- Published
- 2006