(from the application): The purpose of this application is to provide support for studies designed to attempt to identify whether a renewable cell population for melanocytes exists and whether melanocyte precursors with substantial proliferative potential can be isolated and propagated. Inherited diseases such as oculocutaneous albinism and acquired diseases such as vitiligo feature extensive depigmentation of the skin, with resulting morbidity that includes increased sun sensitivity and a greater predisposition to skin cancer. Additionally, many people who suffer from these disorders in certain societies are culturally ostracized. Treatment for these conditions at present is largely ineffective, and current management restricted mainly to preventive measures. One approach to the treatment of these conditions may involve the transfer of autologous or non-autologous melanocyte precursors to these individuals to facilitate the repopulation of their epidermis with normal melanocytes. In inherited pigmentary disorders, techniques of gene transfer may be useful to transfer normal copies of genes mutated in the afflicted individual to melanocyte precursors prior to transfer. To develop these techniques, it is necessary to be able to identify either a melanocyte stem cell population, one capable of unlimited self-renewal, or an undifferentiated melanocyte precursor population capable of substantial proliferation in cell culture. The proposed studies are designed to identify such cell populations, study the requirements for continued cell growth in culture, and identify markers distinguishing them from mature melanocytes that may facilitate their isolation from the adult organism. Hence, these studies will employ a murine model to identify melanocyte stem cell and precursor populations. Existing markers of melanocyte differentiation and transgenic markers will be employed to isolate cells from murine embryos and study their proliferative potential in cell culture. The effects of modifying agents on their proliferative potential will be examined. Finally, markers specific for these cell populations will be identified.
| Lanning, Jessica L; Wallace, Jaclyn S; Zhang, Deming et al. (2005) Altered melanocyte differentiation and retinal pigmented epithelium transdifferentiation induced by Mash1 expression in pigment cell precursors. J Invest Dermatol 125:805-17 |
| Jiao, Zhongxian; Mollaaghababa, Ramin; Pavan, William J et al. (2004) Direct interaction of Sox10 with the promoter of murine Dopachrome Tautomerase (Dct) and synergistic activation of Dct expression with Mitf. Pigment Cell Res 17:352-62 |
| Hornyak, T J; Hayes, D J; Chiu, L Y et al. (2001) Transcription factors in melanocyte development: distinct roles for Pax-3 and Mitf. Mech Dev 101:47-59 |
| Hornyak, T J; Hayes, D J; Ziff, E B (2000) Cell-density-dependent regulation of expression and glycosylation of dopachrome tautomerase/tyrosinase-related protein-2. J Invest Dermatol 115:106-12 |
