Department of Dermatology, Boston University School of Medicine, 609 Albany Street, Boston, MA 02118, USA.
Cell Death Differ. 2012 Apr;19(4):616-22. doi: 10.1038/cdd.2011.132. Epub 2011 Oct 14.
PAX3 (paired box 3) is known to have an important role in melanocyte development through modulation of microphthalmia-associated transcription factor transcription. Here we found that PAX3 transcriptional activity could be regulated through FGF2 (basic fibroblast growth factor)-STAT3 (signal transducer and activator of transcription 3) signaling in the pigment cells. To study its function in vivo, we have generated a transgenic mouse model expressing PAX3 driven by tyrosinase promoter in a tissue-specific fashion. These animals exhibit hyperpigmentation in the epidermis, evident in the skin color of their ears and tails. We showed that the darker skin color results from both increased melanocyte numbers and melanin synthesis. Together, our study delineated a novel pathway in the melanocyte lineage, linking FGF2-STAT3 signaling to increased PAX3 transcription. Moreover, our results suggest that this pathway might contribute to the regulation of melanocyte numbers and melanin levels, and thereby provide an alternative strategy to induce pigmentation.
PAX3（配对盒基因 3）通过调节小眼畸形相关转录因子转录，已知在黑素细胞发育中具有重要作用。在这里，我们发现 PAX3 的转录活性可以通过黑色素细胞中的 FGF2（碱性成纤维细胞生长因子）-STAT3（信号转导和转录激活因子 3）信号通路进行调节。为了在体内研究其功能，我们构建了一种转基因小鼠模型，该模型通过酪氨酸酶启动子以组织特异性方式表达 PAX3。这些动物的表皮出现过度色素沉着，表现在耳朵和尾巴的皮肤颜色上。我们表明，更深的肤色是由于黑素细胞数量和黑色素合成增加所致。总之，我们的研究描绘了黑素细胞谱系中的一条新途径，将 FGF2-STAT3 信号通路与 PAX3 转录的增加联系起来。此外，我们的结果表明，该途径可能有助于调节黑素细胞数量和黑色素水平，从而提供了一种诱导色素沉着的替代策略。
