Antagonistic cross-regulation between Wnt and Hedgehog signalling pathways controls post-embryonic retinal proliferation
Antagonistic cross-regulation between Wnt and Hedgehog signalling pathways controls post-embryonic retinal proliferation
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DOI：
10.1242/dev.079582
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发表时间：
2012-10-01
期刊：
影响因子：
4.6
通讯作者：
Perron, Muriel
中科院分区：
文献类型：
--
作者：
Borday, Caroline;Cabochette, Pauline;Perron, Muriel
成人神经系统中的连续神经发生需要增殖和分化之间的微妙平衡。虽然Wnt/β-连环蛋白和Hedgehog信号通路被认为在成体神经干/祖细胞中具有促有丝分裂功能，但它们在这一过程中如何相互作用仍不清楚。成年两栖动物从位于睫状边缘区（CMZ）的神经干细胞库中产生视网膜神经元。令人惊讶的是，我们发现Wnt和Hedgehog通路的扰动导致CMZ中神经干/祖细胞的相反增殖结果。此外，我们的研究表明，Wnt和刺猬形态发生在胚胎后视网膜的相互排斥的领域。使用遗传和药理学工具，我们发现Wnt和Hedgehog通路表现出相互抑制。我们的数据表明，Sfrp-1和Gli 3有助于这种负交叉调节。总之，我们的研究结果揭示了一个意想不到的Wnt和刺猬信号的拮抗相互作用，可以严格调节神经干/祖细胞增殖的程度在非洲爪蟾视网膜。
Continuous neurogenesis in the adult nervous system requires a delicate balance between proliferation and differentiation. Although Wnt/beta-catenin and Hedgehog signalling pathways are thought to share a mitogenic function in adult neural stem/progenitor cells, it remains unclear how they interact in this process. Adult amphibians produce retinal neurons from a pool of neural stem cells localised in the ciliary marginal zone (CMZ). Surprisingly, we found that perturbations of the Wnt and Hedgehog pathways result in opposite proliferative outcomes of neural stem/progenitor cells in the CMZ. Additionally, our study revealed that Wnt and Hedgehog morphogens are produced in mutually exclusive territories of the post-embryonic retina. Using genetic and pharmacological tools, we found that the Wnt and Hedgehog pathways exhibit reciprocal inhibition. Our data suggest that Sfrp-1 and Gli3 contribute to this negative cross-regulation. Altogether, our results reveal an unexpected antagonistic interplay of Wnt and Hedgehog signals that may tightly regulate the extent of neural stem/progenitor cell proliferation in the Xenopus retina.