Cooperative action of Sox9, Snail2 and PKA signaling in early neural crest development
Cooperative action of Sox9, Snail2 and PKA signaling in early neural crest development
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DOI：
10.1242/dev.02297
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发表时间：
2006-04-01
期刊：
影响因子：
4.6
通讯作者：
Wakamatsu, Y
中科院分区：
文献类型：
--
作者：
Sakai, D;Suzuki, T;Wakamatsu, Y
在神经嵴形成中，转录因子如E组Sox和Snail 1/Snail 2（Slug）调节随后的上皮-间质转化（EMT）和迁移。特别是，Sox 9对颅中神经嵴形成、EMT和嵴衍生软骨的分化具有强烈的影响。然而，目前尚不清楚Sox 9在这些事件中如何发挥作用，以及Sox 9的活性如何调节。在这项研究中，我们的功能获得和功能丧失的实验表明，Sox 9是必不可少的BMP信号介导的诱导蜗牛2和随后的EMT在鸟类神经嵴。我们还表明，蜗牛2激活蜗牛2启动子，虽然蜗牛家族蛋白已被称为阻遏物。一致地，Sox 9与Snail 2协同并通过直接结合Snail 2直接激活Snail 2启动子。最后，这些转录因子在神经嵴细胞中的功能通过PKA信号增强。
In neural crest formation, transcription factors, such as group E Sox and Snail1/Snail2 (Slug) regulate subsequent epithelial-mesenchymal transition (EMT) and migration. In particular, Sox9 has a strong effect on neural crest formation, EMT and differentiation of crest-derived cartilages in the cranium. It remains unclear, however, how Sox9 functions in these events, and how Sox9 activity is regulated. In this study, our gain-of-function and loss-of-function experiments reveal that Sox9 is essential for BMP signal-mediated induction of Snail2 and subsequent EMT in avian neural crest. We also show that Snail2 activates the Snail2 promoter, although Snail family proteins have been known as a repressor. Consistently, Sox9 directly activates the Snail2 promoter in synergy with, and through a direct binding to, Snail2. Finally, functions of these transcription factors in neural crest cells are enhanced by PKA signaling.