Abstract
Early shaping of Xenopus laevis embryos occurs through convergent and extension movements, a process that is driven by intercalation of polarized dorsal mesodermal cells and regulated by non-canonical Wnt signalling1,2,3. Here, we have identified Xenopus syndecan-4 (xSyn4), a cell-surface transmembrane heparan sulphate proteoglycan. At the gastrula stage, xSyn4 is expressed in the involuting dorsal mesoderm and the anterior neuroectoderm. Later, it is found in the pronephros, branchial arches, brain and tailbud. Both gain- and loss-of-function of xSyn4 impaired convergent extension movements in Xenopus embryos and in activin-treated ectodermal explants. xSyn4 interacts functionally and biochemically with the Wnt receptor Frizzled7 (xFz7) and its signal transducer Dishevelled (xDsh). Furthermore, xSyn4 is necessary and sufficient for translocation of xDsh to the plasma membrane — a landmark in the activation of non-canonical Wnt signalling1,2,3. Our results suggest that the ability of xSyn4 to translocate xDsh is regulated by fibronectin, a component of the extracellular matrix required for proper convergent extension movements4,5,6. We propose a model where xSyn4 and fibronectin cooperate with xFz7 and Wnt in the specific activation of the non-canonical Wnt pathway.
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Acknowledgements
We thank O. Wessely, S. Piccolo, E. Brandan, J. Garrido and R. Mayor for comments on the manuscript. We thank S. Fraser, R. Harland, R. Keller, R. Moon and H. Steinbeisser for reagents. J.L. would like to thank E. De Robertis for the great years at UCLA. M.M. is a Comisión Nacional de Investigación, Ciencia y Tecnología (CONICYT) Ph.D. fellow. This work was supported by Fondo Nacional de Ciencia y Tecnología (FONDECYT, 1030481).
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Muñoz, R., Moreno, M., Oliva, C. et al. Syndecan-4 regulates non-canonical Wnt signalling and is essential for convergent and extension movements in Xenopus embryos. Nat Cell Biol 8, 492–500 (2006). https://doi.org/10.1038/ncb1399
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DOI: https://doi.org/10.1038/ncb1399
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