Schouwey Karine, Delmas Véronique, Larue Lionel, Zimber-Strobl Ursula, Strobl Lothar J, Radtke Freddy, Beermann Friedrich
ISREC (Swiss Institute for Experimental Cancer Research), National Center of Competence in Research Molecular Oncology, Epalinges, Switzerland.
Dev Dyn. 2007 Jan;236(1):282-9. doi: 10.1002/dvdy.21000.
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.
Notch信号通路参与多种生物学过程，如细胞命运决定或干细胞维持。在本研究中，我们使用RBP-Jkappa、Notch1和Notch2条件性敲除小鼠评估了该通路在黑素细胞发育和毛发色素沉着中的作用。利用Tyr::Cre小鼠在黑素细胞谱系中使RBP-Jkappa失活来破坏Notch通路，导致毛色严重变淡。同样，当黑素细胞中的Notch1和/或Notch2受体被敲除时，观察到毛发变白。这种表型与floxed Notch等位基因的数量成正比，在Tyr::Cre/°; Notch1(flox/flox); Notch2(flox/flox)小鼠中观察到最明显的效果。在成黑素细胞中缺失Notch1和/或Notch2不会诱发先天性缺陷。胚胎期表达Dct的细胞数量不受影响，但在毛囊首次再生期间，位于毛基质内的黑素细胞逐渐消失。相比之下，非毛囊黑素细胞以及真皮和脉络膜中的色素沉着不受影响。我们认为，Notch1和Notch2受体都有助于维持成黑素细胞和黑素细胞干细胞，并且对正常的毛发色素沉着至关重要。
