Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a
- *Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, and ‡Varmus Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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Contributed by Igor B. Dawid
Abstract
Members of the Wnt family of signaling molecules are expressed differentially along the dorsal–ventral axis of the developing neural tube. Thus we asked whether Wnt factors are involved in patterning of the nervous system along this axis. We show that Wnt-1 and Wnt-3a, both of which are expressed in the dorsal portion of the neural tube, could synergize with the neural inducers noggin and chordin in Xenopus animal explants to generate the most dorsal neural structure, the neural crest, as determined by the expression of Krox-20, AP-2, and slug. Overexpression of Wnt-1 or Wnt-3a in the neuroectoderm of whole embryos led to a dramatic increase of slug and Krox-20-expressing cells, but the hindbrain expression of Krox-20 remained unaffected. Enlargement in the neural crest population could occur even when cell proliferation was inhibited. Wnt-5A and Wnt-8, neither of which is expressed in the dorsal neuroectoderm, failed to induce neural crest markers. Overexpression of glycogen synthase kinase 3, known to antagonize Wnt signaling, blocked the neural-crest-inducing activity of Wnt-3a in animal explants and inhibited neural crest formation in whole embryos. We suggest that Wnt-1 and Wnt-3a have a role in patterning the neural tube along its dorsoventral axis and function in the differentiation of the neural crest.
Footnotes
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↵ † To whom reprint requests should be addressed at: Department of Animal Biology, School of Veterinary Medicine University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104. e-mail: js381m{at}nih.gov.
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↵ § Present address: Division of Neuroscience, Enders 379, Children’s Hospital/Harvard Medical School, Boston, MA 02115.
- ABBREVIATIONS:
- β-gal,
- β-galactosidase;
- BMP,
- bone morphogenetic protein;
- HUA,
- hydroxyurea plus aphidicolin;
- GSK-3,
- glycogen synthase kinase 3
