Transcriptional regulation of mitfa accounts for the sox10 requirement in zebrafish melanophore development
Transcriptional regulation of mitfa accounts for the sox10 requirement in zebrafish melanophore development
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DOI：
10.1242/dev.00461
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发表时间：
2003-06-01
期刊：
影响因子：
4.6
通讯作者：
Kelsh, RN
中科院分区：
文献类型：
--
作者：
Elworthy, S;Lister, JA;Kelsh, RN
转录因子 Sox10 是包括黑素细胞在内的所有非间充质神经嵴衍生物的规范、迁移和存活所必需的。 sox10(-/-) 斑马鱼缺乏转录因子 mitfa 的表达，而该转录因子本身是黑素细胞发育所必需的。我们证明斑马鱼 mitfa 启动子具有体外活性所需的 sox10 结合位点，这与使用哺乳动物细胞培养物进行的研究一致，这些研究表明 Sox10 直接调节 Mitf 表达。此外，我们证明这些位点对于体内启动子活性是必需的。我们发现，在神经嵴细胞中重新引入 mitfa 表达可以挽救 sox10(-/-) 胚胎中黑素细胞的发育。 sox10(-/-) 胚胎中黑色素细胞的拯救在数量上与 mitfa(-/-) 胚胎中的拯救没有区别。这些发现表明，sox10 在黑素细胞发育中的基本功能仅限于 mitfa 的转录调节。我们认为，具有 SOX10 突变的 Waardenburg 综合征 IV 个体中的显性黑素细胞表型可能是由于未能激活正常数量的黑素细胞中的 MITF 造成的。
The transcription factor Sox10 is required for the specification, migration and survival of all nonectomesenchymal neural crest derivatives including melanophores. sox10(-/-) zebrafish lack expression of the transcription factor mitfa, which itself is required for melanophore development. We demonstrate that the zebrafish mitfa promoter has sox10 binding sites necessary for activity in vitro, consistent with studies using mammalian cell cultures that have shown that Sox10 directly regulates Mitf expression. In addition, we demonstrate that these sites are necessary for promoter activity in vivo. We show that reintroduction of mitfa expression in neural crest cells can rescue melanophore development in sox10(-/-) embryos. This rescue of melanophores in sox10(-/-) embryos is quantitatively indistinguishable from rescue in mitfa(-/-) embryos. These findings show that the essential function of sox10 in melanophore development is limited to transcriptional regulation of mitfa. We propose that the dominant melanophore phenotype in Waardenburg syndrome IV individuals with SOX10 mutations is likely to result from failure to activate MITF in the normal number of melanoblasts.