Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development.
Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5A class and by a dominant negative cadherin in early Xenopus development.
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DOI：
10.1083/jcb.133.5.1123
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发表时间：
1996-06
期刊：
影响因子：
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通讯作者：
Moon RT
中科院分区：
文献类型：
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作者：
Torres MA;Yang-Snyder JA;Purcell SM;DeMarais AA;McGrew LL;Moon RT
当在非洲爪蟾胚胎中过表达时，Xwnt-1、-3A、-8和-8b定义了促进胚轴复制的Wnt功能类别（Wnt-1类别），而Xwnt-5A、-4和-11定义了改变形态发生运动的不同类别（Wnt-5A类别）（Du，S.，S.作者：珀塞尔，J. McGrew和R.月球1995.摩尔Cell. 15：2625-2634）。由于在脊椎动物发育过程中，胚胎细胞可能暴露于来自两种功能类型的Wnt的信号，这就提出了这些类型的Wnt的信号传导途径如何相互作用的问题。为了解决这个问题，我们在发育中的非洲爪蟾胚胎中共表达了各种Xwnts和Wnt-1类信号通路的组分。Xwnt-5A类成员拮抗异位Wnt-1类诱导类鹅蛋白表达和次级轴的能力。有趣的是，Wnt-5A类并没有阻止类鹅的表达或轴诱导响应Wnt-1信号通路，β-连环蛋白或激酶死亡gsk-3，或无关的分泌因子，BVg 1的细胞质成分的过表达。Wnt-5A类阻断对Wnt-1类的应答的能力可能涉及细胞粘附的降低，因为Xwnt-5A的异位表达导致Ca 2+依赖性细胞粘附的降低，并且Xwnt-5A阻断Wnt-1类信号的活性被显性负性N-钙粘蛋白模拟。这些数据强调了细胞粘附在调节胚胎细胞对信号分子的反应中的重要性，并表明Wnt-5A功能类信号传导因子可以以拮抗方式与Wnt-1类相互作用。
When overexpressed in Xenopus embryos, Xwnt-1, -3A, -8 and -8b define a functional class of Wnts (the Wnt-1 class) that promotes duplication of the embryonic axis, whereas Xwnt-5A, -4, and -11 define a distinct class (the Wnt-5A class) that alters morphogenetic movements (Du, S., S. Purcell, J. Christian, L. McGrew, and R. Moon. 1995. Mol. Cell. Biol. 15:2625-2634). Since come embryonic cells may be exposed to signals from both functional classes of Wnt during vertebrate development, this raises the question of how the signaling pathways of these classes of Wnts might interact. To address this issue, we coexpressed various Xwnts and components of the Wnt-1 class signaling pathway in developing Xenopus embryos. Members of the Xwnt-5A class antagonized the ability of ectopic Wnt-1 class to induce goosecoid expression and a secondary axis. Interestingly, the Wnt-5A class did not block goosecoid expression or axis induction in response to overexpression of cytoplasmic components of the Wnt-1 signaling pathway, beta-catenin or a kinase-dead gsk-3, or to the unrelated secreted factor, BVg1. The ability of the Wnt-5A class to block responses to the Wnt-1 class may involve decreases in cell adhesion, since ectopic expression of Xwnt-5A leads to decreased Ca2+-dependent cell adhesion and the activity of Xwnt-5A to block Wnt-1 class signals is mimicked by a dominant negative N-cadherin. These data underscore the importance of cell adhesion in modulating the responses of embryonic cells to signaling molecules and suggest that the Wnt-5A functional class of signaling factors can interact with the Wnt-1 class in an antagonistic manner.