We have completed work on this project during the past year. The manuscript describing our work on the regulation of melanocyte development and differentiation by neurofibromin, using a mouse model of type I neurofibromatosis, is nearly complete and is being prepared for publication. The results of this study showed that neurofibromin negatively regulates the Kit - Mitf signaling axis during melanocyte development. They also showed that it suppresses melanogenic gene expression and reduces Kit ligand-dependent MAP kinase activation in differentiated melanocytes. These results are consistent with the hyperpigmented lesions observed in patients with type I neurofibromatosis.The manuscript describing our work on melanocyte development and survival in a mouse model of Waardenburg syndrome is currently in the submission process. In this study, melanocytes in the stria vascularis, a layer of the inner ear whose proper function is dependent upon melanocyte survival, were studied. We found that the survival of strial melanocytes deficient in the transcription factor Mitf could be rescued by the combination of stem cell factor/Kit ligand and the peptide endothelin-3.
