title: The CapZ interacting protein Rcsd1 is required for cardiogenesis downstream of Wnt11a in Xenopus laevis.
abstract: Wnt proteins are critical for embryonic cardiogenesis and cardiomyogenesis by regulating different intracellular signalling pathways. Whereas canonical Wnt/β-catenin signalling is required for mesoderm induction and proliferation of cardiac progenitor cells, β-catenin independent, non-canonical Wnt signalling regulates cardiac specification and terminal differentiation. Although the diverse cardiac malformations associated with the loss of non-canonical Wnt11 in mice such as outflow tract (OFT) defects, reduced ventricular trabeculation, myofibrillar disorganization and reduced cardiac marker gene expression are well described, the underlying molecular mechanisms are still not completely understood. Here we aimed to further characterize Wnt11 mediated signal transduction during vertebrate cardiogenesis. Using Xenopus as a model system, we show by loss of function and corresponding rescue experiments that the non-canonical Wnt signalling mediator Rcsd1 is required downstream of Wnt11 for ventricular trabeculation, terminal differentiation of cardiomyocytes and cardiac morphogenesis. We here place Rcsd1 downstream of Wnt11 during cardiac development thereby providing a novel mechanism for how non-canonical Wnt signalling regulates vertebrate cardiogenesis.
authors.affiliation: Institute of Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany; International Graduate School in Molecular Medicine Ulm, IGradU, Ulm University, 89069 Ulm, Germany.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Hempel
authors.affiliation: Institute of Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany.
authors.forename: Susanne J
authors.initials: SJ
authors.lastname: Kühl
authors.affiliation: Institute of Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany; International Graduate School in Molecular Medicine Ulm, IGradU, Ulm University, 89069 Ulm, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Rothe
authors.affiliation: Institute of Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany; International Graduate School in Molecular Medicine Ulm, IGradU, Ulm University, 89069 Ulm, Germany.
authors.forename: Purushothama
authors.initials: P
authors.lastname: Rao Tata
authors.affiliation: Institute of Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany.
authors.forename: Ioan Ovidiu
authors.initials: IO
authors.lastname: Sirbu
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, BioCenter Oulu and InfoTech Oulu,University of Oulu, Aapistie 5, FIN-90014, Finland.
authors.forename: Seppo J
authors.initials: SJ
authors.lastname: Vainio
authors.affiliation: Institute of Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany. Electronic address: michael.kuehl@uni-ulm.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Kühl
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002454:Cell Differentiation; D003593:Cytoplasm / Q000378:metabolism; D047108:Embryonic Development; D017353:Gene Deletion; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D041681:NIH 3T3 Cells; D038081:Organogenesis; D010641:Phenotype; D011485:Protein Binding; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C000606098:RCSD1 protein, Xenopus; D051153:Wnt Proteins; C508957:Wnt11 protein, mouse; D029867:Xenopus Proteins; C512785:wnt11b protein, Xenopus
keywords: Cardiogenesis; Rcsd1; Wnt11