Regulation of convergent extension movements in Xenopus laevis gastrulation

非洲爪蟾原肠胚形成中会聚伸展运动的调节

• 批准号: 330759792
• 负责人: Dr. Dietmar Gradl
• 金额: --
• 依托单位: Abteilung für Zell- und Entwicklungsbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/330759792?language=en
• 关键词: Regulation; convergent; extension; movements; Xenopus

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.

原肠胚形成和胚层定位涉及复杂的细胞行为，包括由规范和非规范 Wnt 信号级联控制的极化和会聚延伸 (CE) 运动。特别是，CE 运动受到不同 Wnt 触发信号转导途径的协调一致的调节。在此，Wnt11/PCP途径调节中胚层细胞的极化，Wnt5A/Ror2途径调节中胚层细胞向背中线的迁移。 Wnt/β-连环蛋白途径的作用以及调节该过程的不同途径的整合尚不清楚。我们发现 Lef-1 调节小窝核心成分（包括 Caveolin1）的表达，Wnt5A/Ror2 信号传导需要小窝蛋白依赖性内吞作用，并且 Wnt5A 调节 MAPKK pbk 的表达。在这里，我们建议研究由 Lef-1/caveolin、caveolin 介导的 Wnt5A/Ror2 内化和随后 Wnt5A 靶基因 pbk 的 MAPK 调节组成的网络如何在非洲爪蟾原肠胚形成过程中协调 CE 运动。为此，我们将在爪蟾中使用遗传方法，通过受体/配体复合物动力学和摄取的高分辨率成像来证实。