Induction of neural crest in Xenopus by transcription factor AP2alpha

We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2alpha 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 AP2alpha 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. AP2alpha 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 AP2alpha requires some attenuation of endogenous BMP signaling; however, this process occurs at a lower threshold for AP2alpha. Furthermore, AP2alpha expression domains are larger than for other NC factors. Loss-of-function experiments with antisense AP2alpha morpholino oligonucleotides result in severe reduction in the NC territory. These results support a central role for AP2alpha in NC induction. We propose a model in which AP2alpha expression, along with inactivation of NC inhibitory factors such as Dlx3, establish a feedback loop comprising AP2alpha, Sox9, and Slug, leading to and maintaining NC specification.