Indispensable role of Bcl2 in the development of the melanocyte stem cell

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.12.025 Byline: Siu-Shan Mak (a), Mariko Moriyama (a), Eri Nishioka (b), Masatake Osawa (a), Shin-Ichi Nishikawa (a) Keywords: bcl2; bcl2 null; Melanoblast; c-Kit; Hair follicle development; Melanocyte stem cell; Melanocyte survival; Stem cell development; Stem cell factor Abstract: Bcl2 null mice display a characteristic loss of pigmentation demonstrating the importance of Bcl2 in the melanocyte (Mc) lineage. It was recently reported that this abnormal phenotype is due to the failure of melanocyte stem cell (MSC) maintenance and that Bcl2 is selectively important for the survival of MSCs. However, in our analysis of the same mouse, we observe a reduction in melanoblast (Mb) number in both epidermal and follicular populations. More importantly, there is a complete absence of MSCs. SCF downregulation in the epidermis is concomitant with the dramatic reduction in Mb numbers observed in the Bcl2 null, suggesting that Bcl2 is indispensable for the survival of Mbs in the absence of c-Kit signaling. Consistently, abrogation of c-Kit signaling in Bcl2 null mice depletes all Mbs and Mcs, whereas continuous expression of SCF in epidermal keratinocytes rescues the MSCs. Our results demonstrate that Bcl2 has a general role in Mb and Mc survival and is essential for the emergence of MSCs. Moreover, the results indicate that the first wave of Mcs that provide hair pigmentation is derived directly from epidermal Mbs bypassing MSCs. Furthermore, a Bcl2-independent mechanism of action of SCF in the Mc lineage is revealed as SCF c-Kit signaling is functional in the absence of Bcl2. Author Affiliation: (a) RIKEN, Center for Developmental Biology (CDB), Laboratory for Stem Cell Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan (b) Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan Article History: Received 29 July 2005; Revised 6 December 2005; Accepted 9 December 2005