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
Hauptverfasser: PANDUR, Petra, LÄSCHE, Matthias, EISENBERG, Leonard M, KÜHL, Michael
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LÄSCHE, Matthias
EISENBERG, Leonard M
KÜHL, Michael
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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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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