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

在非洲爪蟾细胞粘附依赖会聚延伸（CE）的边缘区是主要的力量，驱动迁移的退化中胚层。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。在第一个资助期间，我们了解到Cam KII是由Xwnt-5A激活的，并且该途径的两个组分都抑制会聚延伸。我们还发现，Xwnt-8信号，包括下游活动的HMG盒转录因子是必需的这个过程中，因为显性负的Lef-1突变体的表达阻断收敛延伸。这两种抑制作用都不能通过XB-钙粘蛋白表达来挽救。这表明Xwnt-5A和Xwnt-8影响对会聚延伸重要的其他分子。为了确定这些组件的一个更详细的分析，这个过程的计划，使抑制作用可以与动态的肌动蛋白或微管细胞骨架和粘附强度。与此同时，我们试图找到两个不同的Xwnt信号级联效应蛋白和它们的目标分子在收敛延伸的过程中进行救援实验与合适的候选分子。

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.