Regulation of convergent extension movements in Xenopus laevis gastrulation

• Applicant: Dr. Dietmar Gradl
• Subject Area: Developmental Biology
• Term: from 2016 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 330759792

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.

• DFG Programme: Research Grants