Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells

• Published in: The Journal of cell biology 2006-05, Vol.173 (3), p.333-339
• Main Authors: Moriyama, Mariko, Osawa, Masatake, Mak, Siu-Shan, Ohtsuka, Toshiyuki, Yamamoto, Norio, Han, Hua, Delmas, Véronique, Kageyama, Ryoichiro, Beermann, Friedrich, Larue, Lionel, Nishikawa, Shin-Ichi
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - physiology; Cell Cycle Proteins - genetics; Cell Survival - drug effects; Cell Survival - physiology; Cellular biology; Dipeptides - pharmacology; Enzyme Inhibitors - pharmacology; Epidermis - cytology; Epidermis - embryology; Epidermis - metabolism; Gene Expression - genetics; Hair; Hair Color - genetics; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Immunoglobulin J Recombination Signal Sequence-Binding Protein - genetics; Intramolecular Oxidoreductases - metabolism; Jagged-2 Protein; Melanocytes - cytology; Melanocytes - metabolism; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mice, Transgenic; Pigments; Receptor, Notch1 - metabolism; Receptors, Notch - physiology; Signal transduction; Signal Transduction - physiology; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transcription Factor HES-1
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200509084

Melanoblasts (Mbs) are thought to be strictly regulated by cell-cell interactions with epidermal keratinocytes, although the precise molecular mechanism of the regulation has been elusive. Notch signaling, whose activation is mediated by cell-cell interactions, is implicated in a broad range of developmental processes. We demonstrate the vital role of Notch signaling in the maintenance of Mbs, as well as melanocyte stem cells (MSCs). Conditional ablation of Notch signaling in the melanocyte lineage leads to a severe defect in hair pigmentation, followed by intensive hair graying. The defect is caused by a dramatic elimination of Mbs and MSCs. Furthermore, targeted overexpression of Hes1 is sufficient to protect Mbs from the elimination by apoptosis. Thus, these data provide evidence that Notch signaling, acting through Hes1, plays a crucial role in the survival of immature Mbs by preventing initiation of apoptosis.