Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis
Formation of the vertebrate heart requires a complex interplay of several temporally regulated signalling cascades. In Xenopus laevis, cardiac specification occurs during gastrulation and requires signals from the dorsal lip and underlying endoderm. Among known Xenopus Wnt genes, only Wnt-11 shows a...
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Veröffentlicht in: | Nature (London) 2002-08, Vol.418 (6898), p.636-641 |
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description | Formation of the vertebrate heart requires a complex interplay of several temporally regulated signalling cascades. In Xenopus laevis, cardiac specification occurs during gastrulation and requires signals from the dorsal lip and underlying endoderm. Among known Xenopus Wnt genes, only Wnt-11 shows a spatiotemporal pattern of expression that correlates with cardiac specification, which indicates that Wnt-11 may be involved in heart development. Here we show, through loss- and gain-of-function experiments, that XWnt-11 is required for heart formation in Xenopus embryos and is sufficient to induce a contractile phenotype in embryonic explants. Treating the mouse embryonic carcinoma stem cell line P19 with murine Wnt-11 conditioned medium triggers cardiogenesis, which indicates that the function of Wnt-11 in heart development has been conserved in higher vertebrates. XWnt-11 mediates this effect by non-canonical Wnt signalling, which is independent of beta-catenin and involves protein kinase C and Jun amino-terminal kinase. Our results indicate that the cardiac developmental program requires non-canonical Wnt signal transduction. |
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In Xenopus laevis, cardiac specification occurs during gastrulation and requires signals from the dorsal lip and underlying endoderm. Among known Xenopus Wnt genes, only Wnt-11 shows a spatiotemporal pattern of expression that correlates with cardiac specification, which indicates that Wnt-11 may be involved in heart development. Here we show, through loss- and gain-of-function experiments, that XWnt-11 is required for heart formation in Xenopus embryos and is sufficient to induce a contractile phenotype in embryonic explants. Treating the mouse embryonic carcinoma stem cell line P19 with murine Wnt-11 conditioned medium triggers cardiogenesis, which indicates that the function of Wnt-11 in heart development has been conserved in higher vertebrates. XWnt-11 mediates this effect by non-canonical Wnt signalling, which is independent of beta-catenin and involves protein kinase C and Jun amino-terminal kinase. Our results indicate that the cardiac developmental program requires non-canonical Wnt signal transduction.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature00921</identifier><identifier>PMID: 12167861</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>3T3 Cells ; Animals ; beta Catenin ; Biological and medical sciences ; Culture Media, Conditioned - pharmacology ; Cytoskeletal Proteins - metabolism ; Embryology: invertebrates and vertebrates. Teratology ; Enzymes ; Fundamental and applied biological sciences. Psychology ; Genes ; Glycoproteins - metabolism ; Heart ; Heart - drug effects ; Heart - embryology ; In Situ Hybridization ; In Vitro Techniques ; JNK Mitogen-Activated Protein Kinases ; Mice ; Mitogen-Activated Protein Kinases - metabolism ; Morphogenesis - drug effects ; Myocardium - cytology ; Myocardium - metabolism ; Organogenesis. Fetal development ; Organogenesis. Physiological fonctions ; Physical growth ; Protein Kinase C - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction - drug effects ; Stem cells ; Stem Cells - drug effects ; Stem Cells - enzymology ; Stem Cells - metabolism ; Trans-Activators - metabolism ; Tumor Cells, Cultured ; Vertebrates ; Wnt Proteins ; Xenopus laevis - embryology ; Xenopus Proteins</subject><ispartof>Nature (London), 2002-08, Vol.418 (6898), p.636-641</ispartof><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Macmillan Journals Ltd. 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Psychology</subject><subject>Genes</subject><subject>Glycoproteins - metabolism</subject><subject>Heart</subject><subject>Heart - drug effects</subject><subject>Heart - embryology</subject><subject>In Situ Hybridization</subject><subject>In Vitro Techniques</subject><subject>JNK Mitogen-Activated Protein Kinases</subject><subject>Mice</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Morphogenesis - drug effects</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Organogenesis. Fetal development</subject><subject>Organogenesis. 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In Xenopus laevis, cardiac specification occurs during gastrulation and requires signals from the dorsal lip and underlying endoderm. Among known Xenopus Wnt genes, only Wnt-11 shows a spatiotemporal pattern of expression that correlates with cardiac specification, which indicates that Wnt-11 may be involved in heart development. Here we show, through loss- and gain-of-function experiments, that XWnt-11 is required for heart formation in Xenopus embryos and is sufficient to induce a contractile phenotype in embryonic explants. Treating the mouse embryonic carcinoma stem cell line P19 with murine Wnt-11 conditioned medium triggers cardiogenesis, which indicates that the function of Wnt-11 in heart development has been conserved in higher vertebrates. XWnt-11 mediates this effect by non-canonical Wnt signalling, which is independent of beta-catenin and involves protein kinase C and Jun amino-terminal kinase. 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subjects | 3T3 Cells Animals beta Catenin Biological and medical sciences Culture Media, Conditioned - pharmacology Cytoskeletal Proteins - metabolism Embryology: invertebrates and vertebrates. Teratology Enzymes Fundamental and applied biological sciences. Psychology Genes Glycoproteins - metabolism Heart Heart - drug effects Heart - embryology In Situ Hybridization In Vitro Techniques JNK Mitogen-Activated Protein Kinases Mice Mitogen-Activated Protein Kinases - metabolism Morphogenesis - drug effects Myocardium - cytology Myocardium - metabolism Organogenesis. Fetal development Organogenesis. Physiological fonctions Physical growth Protein Kinase C - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Signal Transduction - drug effects Stem cells Stem Cells - drug effects Stem Cells - enzymology Stem Cells - metabolism Trans-Activators - metabolism Tumor Cells, Cultured Vertebrates Wnt Proteins Xenopus laevis - embryology Xenopus Proteins |
title | Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis |
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