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Frizzled-7 signalling controls tissue separation during Xenopus gastrulation

Abstract

Cell signalling through Frizzled receptors has evolved to considerable complexity within the metazoans. The Frizzled-dependent signalling cascade comprises several branches, whose differential activation depends on specific Wnt ligands, Frizzled receptor isoforms and the cellular context. In Xenopus laevis embryos, the canonical β-catenin pathway contributes to the establishment of the dorsal–ventral axis1. A different branch, referred to as the planar cell polarity pathway, is essential for cell polarization during elongation of the axial mesoderm by convergent extension2. Here we demonstrate that a third branch of the cascade is independent of Dishevelled function and involves signalling through trimeric G proteins and protein kinase C (PKC). During gastrulation, Frizzled-7 (Fz7)-dependent PKC signalling controls cell-sorting behaviour in the mesoderm. Loss of zygotic Fz7 function results in the inability of involuted anterior mesoderm to separate from the ectoderm, which leads to severe gastrulation defects. This result provides a developmentally relevant in vivo function for the Fz/PKC pathway in vertebrates.

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Figure 1: Antisense morpholino oligonucleotide blocks translation of Xenopus Fz7 mRNA and impairs morphogenesis.
Figure 2: Antisense morpholino oligonucleotide for Xenopus Fz7 inhibits tissue separation behaviour but not convergent extension movements.
Figure 3: Antisense morpholino oligonucleotide for Xenopus Fz7 inhibits phosphorylation of PKCα-Myc.
Figure 4: Xenopus Fz7 induces separation behaviour in animal cap cells.

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Acknowledgements

We thank A. Brändli, I. Dawid, M. Hammerschmidt, P. Klein, M. Kühl, R. Moon, W. Reintsch, U. Rothbächer, R. Rupp, D. L. Shi and S. Sokol for providing plasmids; U. Müller for technical assistance; and S. Cramton for critically reading the manuscript. This work was supported by a pre-doctoral fellowship from the Deutscher Akademischer Austanschdienst (DAAD) to A.M. and by a Deutsche Forschungsgemeinschaft (DFG) grant to R.W.

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Winklbauer, R., Medina, A., Swain, R. et al. Frizzled-7 signalling controls tissue separation during Xenopus gastrulation. Nature 413, 856–860 (2001). https://doi.org/10.1038/35101621

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