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Wnt 赢得了这场战争:Wnt 对 Shh 的拮抗作用控制了脊椎动物神经管的背腹模式形成。

Wnt won the war: antagonistic role of Wnt over Shh controls dorso-ventral patterning of the vertebrate neural tube.

机构信息

Institute for Research in Biomedicine, Parc Cientific de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Department of Cell Biology, University of Barcelona, Barcelona, Spain.

出版信息

Dev Dyn. 2010 Jan;239(1):69-76. doi: 10.1002/dvdy.22058.

Abstract

The spinal cord has been used as a model to dissect the mechanisms that govern the patterning of tissues during animal development, since the principles that rule the dorso-ventral patterning of the neural tube are applicable to other systems. Signals that determine the dorso-ventral axis of the spinal cord include Sonic hedgehog (Shh), acting as a bona fide morphogenetic signal to determine ventral progenitor identities, and members of the Bmp and the Wnt families, acting in the dorsal neural tube. Although Wnts have been initially recognized as important in proliferation of neural progenitor cells, their role in the dorso-ventral patterning has been controversial. In this review, we discuss recent reports that show an important contribution of the Wnt canonical pathway in dorso-ventral pattern formation. These data allow building a model by which the ventralizing activity of Shh is antagonized by Wnt activity through the expression of Gli3, a potent inhibitor of the Shh pathway. Therefore, antagonistic interactions between canonical Wnt, promoting dorsal identities, and Shh pathways, inducing ventral ones, would define the dorso-ventral patterning of the developing central nervous system.

摘要

脊髓已被用作模型来剖析在动物发育过程中控制组织模式形成的机制,因为支配神经管背腹模式形成的原则适用于其他系统。决定脊髓背腹轴的信号包括 Sonic hedgehog(Shh),它作为确定腹侧祖细胞身份的真正形态发生信号,以及 Bmp 和 Wnt 家族的成员,在背神经管中起作用。虽然 Wnts 最初被认为在神经祖细胞的增殖中很重要,但它们在背腹模式形成中的作用一直存在争议。在这篇综述中,我们讨论了最近的报道,这些报道显示 Wnt 经典途径在背腹模式形成中具有重要贡献。这些数据允许构建一个模型,其中 Shh 的腹侧化活性通过Gli3 的表达被 Wnt 活性拮抗,Gli3 是 Shh 途径的有效抑制剂。因此,经典 Wnt 的拮抗相互作用,促进背侧特征,和 Shh 途径,诱导腹侧特征,将定义发育中中枢神经系统的背腹模式形成。

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