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

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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.