Regulation of convergent extension movements in Xenopus laevis gastrulation

胚层的形成和定位涉及复杂的细胞行为，包括由经典和非经典Wnt信号级联控制的极化和会聚延伸（CE）运动。特别是，CE运动是由不同的Wnt触发的信号转导通路的管弦乐队。在此，Wnt 11/PCP途径调节中胚层细胞的极化，Wnt 5A/Ror 2途径调节它们向背中线的迁移。Wnt/β-连环蛋白通路的作用和调节该过程的不同通路的整合仅知之甚少。我们发现Lef-1调节小窝核心成分包括小窝蛋白1的表达，Wnt 5A/Ror 2信号传导需要小窝蛋白依赖的内吞作用，并且Wnt 5A调节MAPKK pbk的表达。在这里，我们建议调查如何组成的网络Lef-1/小窝蛋白，小窝蛋白介导的Wnt 5A/Ror 2的内化和随后的Wnt 5A靶基因pbk的MAPK调节编排在非洲爪蟾原肠胚CE运动。为此，我们将使用遗传方法在非洲爪蟾证实了高分辨率成像的受体/配体复合物的动力学和摄取。

Gastrulation and positioning of the germ-layers involves complex cell behaviors including polarization and convergent-extension (CE) movements controlled by canonical and non-canonical Wnt signaling cascades. In particular, CE movements are regulated by an orchestre of different Wnt-triggered signal transduction pathways. Herein, the Wnt11/PCP pathway regulates polarization of the mesodermal cells, the Wnt5A/Ror2 pathway their migration towards the dorsal midline. The role of the Wnt/beta-Catenin pathway and the integration of differnt pathways regulating this process is only poorly unterstood. We found that Lef-1 regulates the expression of caveolae core components including caveolin1, that Wnt5A/Ror2 signaling requires caveolin dependent endocytosis and that Wnt5A regulates the expression of the MAPKK pbk. Here we propose to investigate how a network consisting of Lef-1/caveolin, caveolin mediated Wnt5A/Ror2 internalization and subsequent MAPK regulation by the Wnt5A target gene pbk orchestrates CE movements during Xenopus gastrulation. For this we will use a genetic approach in Xenopus substantiated by high resolution imaging of receptor/ligand complex dynamics and uptake.