Fgf8a induces neural crest indirectly through the activation of Wnt8 in the paraxial mesoderm.
Fgf8a induces neural crest indirectly through the activation of Wnt8 in the paraxial mesoderm.
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DOI：
10.1242/dev.026229
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Saint-Jeannet JP
中科院分区：
文献类型：
--
作者：
Hong CS;Park BY;Saint-Jeannet JP
两个独立的信号是非洲爪哇诱导神经峰(NC)所必需的，一个是BMP信号，它必须被BMP拮抗剂部分减弱，另一个信号是由典型的Wnt或成纤维细胞生长因子介导的。NC形成区域下面的中胚层被认为是第二个信号的来源。WNT8和Fgf8a在NC诱导时在该组织中表达，因此是很好的NC诱导剂。功能丧失研究表明，这些配体都是指定NC所必需的，然而，目前尚不清楚这些信号分子是以相同的途径还是平行的途径操作来产生NC。在这里，我们描述了解决这个悬而未决问题的实验。我们发现，虽然Wnt8的表达可以恢复Fgf8a缺失的胚胎中的NC祖细胞，但Fgf8a无法挽救Wnt8缺失的胚胎中NC的形成。此外，联合注射WNT8或β-Catenin Morolino可强烈抑制Fgf8a在神经化外植体中的NC诱导活性，表明这两个信号分子的活性是连锁的。与这些观察结果一致的是，在整个胚胎和动物外植体中，Fgf8a都是WNT8的有效诱导者，而Fgf8a的敲除导致WNT8在中胚层中的表达显著丧失。我们认为，Fgf8a通过激活旁轴中胚层中的Wnt8间接诱导NC，进而促进BMP拮抗剂启动的上覆外胚层中NC的形成。
Two independent signals are necessary for neural crest (NC) induction in Xenopus, a Bmp signal, which must be partially attenuated by Bmp antagonists and a separate signal mediated either by a canonical Wnt or Fgf. The mesoderm underlying the NC-forming region has been proposed as a source of this second signal. Wnt8 and Fgf8a are expressed in this tissue around the time of NC induction and are therefore good candidate NC inducers. Loss-of-function studies indicate that these ligands are both necessary to specify the NC, however it is unclear whether these signaling molecules are operating in the same or in parallel pathways to generate the NC. Here we describe experiments addressing this outstanding question. We show that while Wnt8 expression can restore NC progenitors in Fgf8a-deficient embryos, Fgf8a is unable to rescue NC formation in Wnt8-depleted embryos. Moreover, the NC-inducing activity of Fgf8a in neuralized explants is strongly repressed by co-injection of Wnt8 or β-catenin morpholino, suggesting that the activity of these two signaling molecules is linked. Consistent with these observations Fgf8a is a potent inducer of Wnt8 in both whole embryos and animal explants, and Fgf8a knockdown results in a dramatic loss of Wnt8 expression in the mesoderm. We propose that Fgf8a induces NC indirectly through the activation of Wnt8 in the paraxial mesoderm, which in turn promotes NC formation in the overlying ectoderm primed by Bmp antagonists.
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