Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis
Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis
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Wls 介导的 Wnt 差异调节远端肢体模式和组织形态发生。
DOI：
10.1016/j.ydbio.2012.02.019
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发表时间：
2012-05-15
影响因子：
2.7
通讯作者：
Guo, Xizhi
中科院分区：
文献类型：
--
作者：
Zhu, Xuming;Zhu, Huang;Guo, Xizhi
Wnt蛋白是一种可扩散的形态发生蛋白，在脊椎动物肢体发育过程中起着多种作用。然而，Wnt信号级联的复杂性和它们的重叠表达阻止了我们解剖它们在肢体模式和组织形态发生中的功能。Wnt基因是各种Wnt分泌所必需的，Wnt基因的缺失使得有可能从基因上剖析Wnt在肢体发育中的整体作用。在这项研究中，Wls基因在肢体间充质和外胚层中被有条件地耗尽。间充质Wls的丧失阻止了远端间充质的分化并阻止了肢体的生长，这很可能是通过影响Wnt 5a功能实现的。同时，外胚层Wls的缺失导致远端肢体组织发育不全和远端间充质的过早退化。这些观察结果表明，Wnt从两个胚层差异调节池的未分化的远端肢体间充质细胞。细胞行为分析显示，外胚层Wnt以不同于FGF的方式维持间充质细胞增殖和存活。外胚层Wnt也首次被证明对肢体中的远端肌腱/韧带诱导、成肌细胞迁移和真皮形成是必不可少的。这些研究结果提供了一个全面的看法，WNTS在肢体图案和组织形态发生的作用。(C)2012 Elsevier Inc. All rights reserved.
Wnt proteins are diffusible morphogens that play multiple roles during vertebrate limb development. However, the complexity of Wnt signaling cascades and their overlapping expression prevent us from dissecting their function in limb patterning and tissue morphogenesis. Depletion of the Wntless (Wls) gene, which is required for the secretion of various Wnts, makes it possible to genetically dissect the overall effect of Wnts in limb development. In this study, the Wls gene was conditionally depleted in limb mesenchyme and ectoderm. The loss of mesenchymal Wls prevented the differentiation of distal mesenchyme and arrested limb outgrowth, most likely by affecting Wnt5a function. Meanwhile, the deletion of ectodermal Wls resulted in agenesis of distal limb tissue and premature regression of the distal mesenchyme. These observations suggested that Wnts from the two germ layers differentially regulate the pool of undifferentiated distal limb mesenchyme cells. Cellular behavior analysis revealed that ectodermal Wnts sustain mesenchymal cell proliferation and survival in a manner distinct from Fgf. Ectodermal Wnts were also shown for the first time to be essential for distal tendon/ligament induction, myoblast migration and dermis formation in the limb. These findings provide a comprehensive view of the role of Wnts in limb patterning and tissue morphogenesis. (C) 2012 Elsevier Inc. All rights reserved.