期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：2
页码：532-537
DOI：10.1073/pnas.0237226100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2 is positively regulated by bone morphogenetic protein (BMP) and Wnt signaling, and that this activation is an essential step in the induction of neural crest (NC). Ectopic expression of AP2 is sufficient to activate high-level expression of NC-specific genes such as Slug and Sox9, which can occur as isolated domains within the neural plate as well as by expansion of endogenous NC territories. AP2 also has the property of inducing NC in isolated ectoderm in which Wnt signaling is provided but BMP signaling is minimized by overexpression of chordin. Like other NC regulatory factors, activation of AP2 requires some attenuation of endogenous BMP signaling; however, this process occurs at a lower threshold for AP2. Furthermore, AP2 expression domains are larger than for other NC factors. Loss-of-function experiments with antisense AP2 morpholino oligonucleotides result in severe reduction in the NC territory. These results support a central role for AP2 in NC induction. We propose a model in which AP2 expression, along with inactivation of NC inhibitory factors such as Dlx3, establish a feedback loop comprising AP2, Sox9, and Slug, leading to and maintaining NC specification.
