Saint-Jeannet J P, He X, Varmus H E, Dawid I B
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13713-8. doi: 10.1073/pnas.94.25.13713.
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.
信号分子Wnt家族的成员在发育中的神经管背腹轴上呈差异表达。因此，我们探究Wnt因子是否参与了沿此轴的神经系统模式形成。我们发现，在非洲爪蟾动物外植体中，均在神经管背侧部分表达的Wnt-1和Wnt-3a，可与神经诱导因子头蛋白和脊索蛋白协同作用，生成最靠背侧的神经结构——神经嵴，这是由Krox-20、AP-2和slug的表达所确定的。在整个胚胎的神经外胚层中过表达Wnt-1或Wnt-3a，会导致表达slug和Krox-20的细胞显著增加，但Krox-20在后脑的表达不受影响。即使细胞增殖受到抑制，神经嵴细胞群也会扩大。在背侧神经外胚层中均不表达的Wnt-5A和Wnt-8，无法诱导神经嵴标志物的表达。已知糖原合酶激酶3可拮抗Wnt信号，其过表达会阻断Wnt-3a在动物外植体中的神经嵴诱导活性，并抑制整个胚胎中的神经嵴形成。我们认为，Wnt-1和Wnt-3a在沿神经管背腹轴的模式形成中发挥作用，并在神经嵴的分化中起作用。
