title: Role of glypican 4 in the regulation of convergent extension movements during gastrulation in Xenopus laevis.
abstract: Coordinated morphogenetic cell movements during gastrulation are crucial for establishing embryonic axes in animals. Most recently, the non-canonical Wnt signaling cascade (PCP pathway) has been shown to regulate convergent extension movements in Xenopus and zebrafish. Heparan sulfate proteoglycans (HSPGs) are known as modulators of intercellular signaling, and are required for gastrulation movements in vertebrates. However, the function of HSPGs is poorly understood. We analyze the function of Xenopus glypican 4 (Xgly4), which is a member of membrane-associated HSPG family. In situ hybridization revealed that Xgly4 is expressed in the dorsal mesoderm and ectoderm during gastrulation. Reducing the levels of Xgly4 inhibits cell-membrane accumulation of Dishevelled (Dsh), which is a transducer of the Wnt signaling cascade, and thereby disturbs cell movements during gastrulation. Rescue analysis with different Dsh mutants and Wnt11 demonstrated that Xgly4 functions in the non-canonical Wnt/PCP pathway, but not in the canonical Wnt/beta-catenin pathway, to regulate gastrulation movements. We also provide evidence that the Xgly4 protein physically binds Wnt ligands. Therefore, our results suggest that Xgly4 functions as positive regulator in non-canonical Wnt/PCP signaling during gastrulation.
authors.affiliation: Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Bisei
authors.initials: B
authors.lastname: Ohkawara
authors.forename: Takamasa S
authors.initials: TS
authors.lastname: Yamamoto
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tada
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D000072261:Dishevelled Proteins; D005775:Gastrula / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000502:physiology; D015027:Zebrafish / Q000502:physiology; D029961:Zebrafish Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; C492044:GPC4 protein, human; D006023:Glycoproteins; D053673:Glypicans; C492043:Gpc4 protein, Xenopus; D019812:Heparan Sulfate Proteoglycans; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D051153:Wnt Proteins; C092568:Wnt11 protein, zebrafish; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C512785:wnt11b protein, Xenopus