Diversin regulates heart formation and gastrulation movements in development.
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.
Moeller
Heinz
H
Max Delbrueck Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13092 Berlin, Germany.
Jenny
Andreas
A
Schaeffer
Hans-Joerg
HJ
Schwarz-Romond
Thomas
T
Mlodzik
Marek
M
Hammerschmidt
Matthias
M
Birchmeier
Walter
W
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*
D003598:Cytoskeletal Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C464905:ankrd6b protein, zebrafish; D048031:JNK Mitogen-Activated Protein Kinases