Cooperative action of Sox9, Snail2 and PKA signaling in early neural crest development.
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.
Sakai
Daisuke
D
Center for Translational and Advanced Animal Research on Human Diseases, Division of Developmental Neuroscience, Graduate School of Medicine, Tohoku University, Sendai, Miyagi 980-8575, Japan.
Suzuki
Takashi
T
Osumi
Noriko
N
Wakamatsu
Yoshio
Y
D000818:Animals; D002454:Cell Differentiation; D003370:Coturnix / Q000196:embryology; D024202:Electrophoretic Mobility Shift Assay; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D008954:Models, Biological; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism*; D009924:Organ Culture Techniques; D010590:Phalloidine; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D005456:Fluorescent Dyes; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D010590:Phalloidine; D008156:Luciferases