Molecular control of cell migration during gastrulation by different members of the Xwnt family

Xwnt家族不同成员对原肠胚形成过程中细胞迁移的分子控制

• 批准号: 5110912
• 负责人: Professorin Dr. Doris Wedlich
• 金额: --
• 依托单位: Abteilung für Zell- und Entwicklungsbiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1998
• 资助国家: 德国
• 起止时间: 1997-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5110912?language=en
• 关键词: Molecular; control; cell; migration; during

In Xenopus cell adhesion dependent convergent extension (CE) of the marginal zone is the main force that drives migration of the involuting mesoderm. We try to identify the molecular mechanisms by which Xwnt-8 and Xwnt-5A control this type of cell movement. During the first funding period we learned that Cam KII is activated by Xwnt-5A and both components of this pathway inhibit convergent extension. We also found that Xwnt-8 signalling including the downstream activity of the HMG-box transcription factor is required for this process because expression of dominant-negative Lef-1 mutants blocked convergent extension. Both inhibitory effects could not be rescued by XB-cadherin expression. This indicates that Xwnt-5A and Xwnt-8 influence other molecules important for convergent extension. To identify these components a more detailed analysis of this process is planned so that the inhibitory effects can be correlated to dynamics of the actin or microtubuli cytoskeleton and adhesion strength. In parallel, we try to find the effector proteins of both different Xwnt-signalling cascades and their targets molecules in the process of convergent extension by performing rescue experiments with suitable candidate molecules.

在非洲爪蛙细胞中，边缘带的黏附依赖会聚延伸(CE)是驱动退化中胚层迁移的主要力量。我们试图确定XWNT-8和XWNT-5A控制这种类型的细胞运动的分子机制。在第一个资助期，我们了解到CaM KII被Xwnt-5A激活，这一通路的两个组成部分都抑制了收敛延伸。我们还发现，Xwnt-8信号包括HMG-box转录因子的下游活性是这一过程所必需的，因为显性负向Lef-1突变体的表达阻止了收敛延伸。这两种抑制作用都不能被XB-钙粘蛋白的表达所挽救。这表明XWNT-5A和XWNT-8影响了其他对收敛延伸很重要的分子。为了确定这些成分，计划对这一过程进行更详细的分析，以便抑制作用可以与肌动蛋白或微管细胞骨架的动力学和黏附强度相关联。同时，我们通过与合适的候选分子进行救援实验，试图找到不同XWNT信号级联的效应蛋白及其靶分子在收敛延伸过程中的作用。