Compartment-dependent activities of Wnt3a/β-catenin signaling during vertebrate axial extension
Compartment-dependent activities of Wnt3a/β-catenin signaling during vertebrate axial extension
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DOI：
10.1016/j.ydbio.2014.08.012
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发表时间：
2014-10-15
影响因子：
2.7
通讯作者：
Mallo, Moises
中科院分区：
文献类型：
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作者：
Jurberg, Arnon Dias;Aires, Rita;Mallo, Moises
脊椎动物体的延伸是胚胎后端许多信号协同活动的结果。其中，Wnt 3a已被证明在轴向祖细胞活性、中胚层形成和体节发生的调节中发挥相关作用。然而，其对轴向生长的影响仍有待充分了解。在小鼠中使用转基因方法，我们发现Wnt 3a信号传导的效果取决于靶组织。高水平的Wnt 3a在上胚层防止神经组织的形成，但不损害轴向祖细胞产生不同的中胚层谱系。即使在严重畸形的胚胎中，这些中胚层组织也保持着显著的组织化程度。然而，从那些没有采取神经命运的细胞中，只有那些离开上胚层上皮层的细胞激活了中胚层程序。剩余的组织积累为折叠的上皮，保持了一些外胚层样特征。结合先前发表的观察结果，我们的研究结果表明Wnt 3a在调节外胚层轴向祖细胞分化命运的更新和选择之间的平衡中具有剂量依赖性作用。在近轴中胚层中，Wnt/β-catenin信号的适当调节不仅是体节发生所必需的，而且也是为体节提供适当的前后极性所必需的。这两个过程似乎依赖于Wnt/β-连环蛋白信号传导的反馈调节的不同要求的机制，一旦分割发生在存在高水平的Wnt 3a的前体中胚层，但不是永久表达的组成型活性形式的β-连环蛋白。总之，我们的研究结果表明，Wnt 3a/β-连环蛋白信号在后延伸过程中起着顺序作用，这强烈依赖于靶组织。这提供了一个额外的例子，说明信号系统的功能输出在多大程度上取决于响应细胞的能力。(C)2014年爱思唯尔公司All rights reserved.
Extension of the vertebrate body results from the concerted activity of many signals in the posterior embryonic end. Among them, Wnt3a has been shown to play relevant roles in the regulation of axial progenitor activity, mesoderm formation and somitogenesis. However, its impact on axial growth remains to be fully understood. Using a transgenic approach in the mouse, we found that the effect of Wnt3a signaling varies depending on the target tissue. High levels of Wnt3a in the epiblast prevented formation of neural tissues, but did not impair axial progenitors from producing different mesodermal lineages. These mesodermal tissues maintained a remarkable degree of organization, even within a severely malformed embryo. However, from the cells that failed to take a neural fate, only those that left the epithelial layer of the epiblast activated a mesodermal program. The remaining tissue accumulated as a folded epithelium that kept some epiblast-like characteristics. Together with previously published observations, our results suggest a dose-dependent role for Wnt3a in regulating the balance between renewal and selection of differentiation fates of axial progenitors in the epiblast. In the paraxial mesoderm, appropriate regulation of Wnt/beta-catenin signaling was required not only for somitogenesis, but also for providing proper anterior posterior polarity to the somites. Both processes seem to rely on mechanisms with different requirements for feedback modulation of Wnt/beta-catenin signaling, once segmentation occurred in the presence of high levels of Wnt3a in the presomitic mesoderm, but not after permanent expression of a constitutively active form of beta-catenin. Together, our findings suggest that Wnt3a/beta-catenin signaling plays sequential roles during posterior extension, which are strongly dependent on the target tissue. This provides an additional example of how much the functional output of signaling systems depends on the competence of the responding cells. (C) 2014 Elsevier Inc. All rights reserved.