title: The Xenopus Tgfbi is required for embryogenesis through regulation of canonical Wnt signalling.
abstract: Tgfbi, a fasciclin family extracellular matrix protein, has various roles in human diseases from corneal dystrophies to cancer. However, the molecular mechanisms that underlie its functions are poorly understood. Here, we studied the role of Tgfbi during Xenopus embryogenesis. During gastrulation and immediately after, Xtgfbi is expressed at developmentally important signaling centers including the dorsal marginal zone, notochord and floorplate. Xtgfbi knockdown by anti-sense morpholinos causes defective organizer induction, patterning and differentiation of muscle, neuron and neural crests, similar to suppression of canonical Wnt signaling. In Xenopus embryos and animal caps as well as DLD-1 cells, we show that Tgfbi is strongly required for the full activation of the canonical Wnt pathway by promoting phosphorylation of GSK3β and consequently enhancing the stabilization and nuclear localization of β-catenin. Further analysis shows that Tgfbi is likely to promote GSK3β phosphorylation through integrin-linked kinase.
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Wanzhou
authors.initials: W
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Xian
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Ohnuma
authors.forename: James D
authors.initials: JD
authors.lastname: Brenton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D055550:Protein Stability; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D038362:Glycogen Synthase Kinase 3; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D051176:beta Catenin; D000099222:betaIG-H3 Protein; C495266:CTNNB1 protein, Xenopus; C581760:GSK3B protein, Xenopus