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Development. 2006 Apr;133(7):1323-33. Epub 2006 Mar 1.

Cooperative action of Sox9, Snail2 and PKA signaling in early neural crest development.

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  • 1Center for Translational and Advanced Animal Research on Human Diseases, Division of Developmental Neuroscience, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan.


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.

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