Syndecan-4 regulates non-canonical Wnt signalling and is essential for convergent and extension movements in Xenopus embryos.
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 signalling. 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 signalling. 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 movements. We propose a model where xSyn4 and fibronectin cooperate with xFz7 and Wnt in the specific activation of the non-canonical Wnt pathway.
Muñoz
Rosana
R
Department of Cell and Molecular Biology, Center for Cell Regulation and Pathology, Millennium Nucleus in Developmental Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile.
Moreno
Mauricio
M
Oliva
Carlos
C
Orbenes
Claudio
C
Larraín
Juan
J
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D053671:Syndecan-4; D051153:Wnt Proteins / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D005353:Fibronectins; C492040:Fzd7 protein, Xenopus; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D053671:Syndecan-4; D051153:Wnt Proteins; D029867:Xenopus Proteins