Regulation of Melanocyte Development and Differentiation

该手稿描述了我们的工作的黑素细胞的发育和分化的神经纤维蛋白的调节，使用小鼠模型的I型神经纤维瘤，目前正在为细胞科学杂志的小修订。本研究的结果表明，在黑素细胞发育过程中，神经纤维蛋白负调控Kit-Mitf信号轴。他们还建立了神经纤维蛋白作为一个重要的调节色素沉着。尽管事实上，我们表明，抑制MAP激酶级联反应具有相反的影响后，在原代黑素细胞的色素酶基因的表达相比，永生化的黑素细胞，神经纤维蛋白的损失的反应是相当的，这表明它是占主导地位的MAP激酶信号通路的扰动，在调节色素沉着。我们的研究结果有助于解释在I型神经纤维瘤病患者中观察到的色素沉着病变的分子基础。描述我们在Waardenburg综合征小鼠模型中黑素细胞发育和存活的工作的手稿目前正在提交过程中。在这项研究中，研究了血管纹中的黑色素细胞，血管纹是内耳的一层，其正常功能取决于黑色素细胞的存活。我们发现，在转录因子Mitf缺乏的黑色素细胞的生存可以通过干细胞因子/试剂盒配体和肽内皮素-3的组合来拯救。这些结果有助于解释一个重要的差异之间的严重的耳色素沉着表型和相对温和的皮肤色素沉着表型中观察到的遗传性发育性色素沉着疾病Waardenburg综合征和Tietz综合征的个人。与本项目主题相关的其他合作工作也旨在进一步了解Mitf转录在减轻黑素细胞对紫外线照射的凋亡反应中的作用。

The manuscript describing our work on the regulation of melanocyte development and differentiation by neurofibromin, using a mouse model of type I neurofibromatosis, is currently under minor revision for the Journal of Cell Science. The results of this study showed that neurofibromin negatively regulates the Kit - Mitf signaling axis during melanocyte development. They also establish neurofibromin as an important regulator of pigmentation. Despite the fact that we showed that inhibition of the MAP kinase cascade has opposing effects upon the expression of pigmentary enzyme genes in primary melanocytes compared to immortalized melanocytes, the response to loss of neurofibromin is comparable, suggesting that it is dominant to perturbations of the MAP kinase signaling pathway in regulating pigmentation. Our results help to explain the molecular basis of 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. These results help to explain an important disparity between the severe otic pigmentary phenotype and the relatively mild cutaneous pigmentary phenotypes observed in individuals with the inherited developmental pigmentary disorders Waardenburg syndrome and Tietz syndrome. Additional collaborative work associated with the theme of this project also is designed to understand further the role of the Mitf transcription in mitigating the apoptotic response of melanocytes to ultraviolet irradiation.