Induction of neural crest in Xenopus by transcription factor AP2α
- *Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and †Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104
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Communicated by Igor B. Dawid, National Institutes of Health, Bethesda, MD (received for review September 23, 2002)
Abstract
We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2α 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 AP2α 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. AP2α 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 AP2α requires some attenuation of endogenous BMP signaling; however, this process occurs at a lower threshold for AP2α. Furthermore, AP2α expression domains are larger than for other NC factors. Loss-of-function experiments with antisense AP2α morpholino oligonucleotides result in severe reduction in the NC territory. These results support a central role for AP2α in NC induction. We propose a model in which AP2α expression, along with inactivation of NC inhibitory factors such as Dlx3, establish a feedback loop comprising AP2α, Sox9, and Slug, leading to and maintaining NC specification.
Footnotes
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↵ ‡ To whom correspondence should be addressed. E-mail: tsargent{at}nih.gov.
- Abbreviations:
- NC,
- neural crest;
- BMP,
- bone morphogenetic protein;
- MO,
- morpholino oligonucleotide;
- Chd,
- chordin
- Copyright © 2003, The National Academy of Sciences
