The Notch pathway: hair graying and pigment cell homeostasis
Karine Schouwey1,2 and Friedrich Beermann1,2
1ISREC (Swiss Institute of Experimental Cancer Research), and 2Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Life Sciences, Epalinges, Switzerland.
Offprint requests to: Dr. Friedrich Beermann, ISREC-EPFL, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland. e-mail: Friedrich.Beermann@isrec.ch
Summary. The Notch signaling pathway is an essential cell-cell interaction mechanism, which regulates processes such as cell proliferation, cell fate decisions, differentiation or stem cell maintenance. Pigmentation in mammals is provided by melanocytes, which are derived from the neural crest, and by the retinal pigment epithelium (RPE), which is part of the optic cup and hence orginates from neuroectoderm. The importance of functional Notch signaling in melanocytes has been unveiled recently. Here, the pathway is essential for the maintenance of proper hair pigmentation. Deletion of Notch1 and Notch2 or RBP-Jκ in the melanocyte lineage resulted in a gene dosage-dependent precocious hair graying, due to the elimination of melanoblasts and melanocyte stem cells. Expression data support the idea that Notch signaling might equally be involved in development of the RPE. Furthermore, recent analyses indicate a possible role of Notch signaling in the development of melanoma. In this review, we address the essential role of Notch signaling in the regeneration of the melanocyte population during hair follicle cycles, and discuss data supporting the implication of this signaling pathway in RPE development and melanoma. Histol Histopathol 23, 609-619 (2008)
Key words: Melanocytes, Notch, RPE, Knockout, Melanoma, Graying