title: Diversin regulates heart formation and gastrulation movements in development.
abstract: Canonical and noncanonical Wnt signaling regulate crucial events in the development of vertebrates and invertebrates. In this work we show that vertebrate Diversin, a potential orthologue of Drosophila Diego, controls fusion of heart precursors and gastrulation movements in zebrafish embryogenesis. These events are regulated by noncanonical Wnt signaling, which is independent of beta-catenin. We found that Diversin directly interacts with Dishevelled and that this interaction is necessary and sufficient to mediate signals of the noncanonical Wnt pathway to downstream effectors like Rho family GTPases and Jun N-terminal kinase. The ankyrin repeats of Diversin are required for the interaction with Dishevelled, for the activation of noncanonical Wnt signaling, and for the biological responses. The mutation K446M in the DEP domain of vertebrate Dishevelled, which mimics a classical Drosophila loss of function mutation, prevents functional interaction with Diversin's ankyrin repeats. Diversin also affects planar cell polarity in Drosophila, which is controlled by the noncanonical Wnt signaling pathway. Our data thus demonstrate that Diversin and Dishevelled function together in a mutually dependent fashion in zebrafish gastrulation and organ formation.
authors.affiliation: Max Delbrueck Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13092 Berlin, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Moeller
authors.forename: Andreas
authors.initials: A
authors.lastname: Jenny
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Schaeffer
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz-Romond
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
authors.forename: Matthias
authors.initials: M
authors.lastname: Hammerschmidt
authors.forename: Walter
authors.initials: W
authors.lastname: Birchmeier
mesh_terms: D000818:Animals; D017089:Ankyrin Repeat; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C464905:ankrd6b protein, zebrafish; D048031:JNK Mitogen-Activated Protein Kinases