Wnt-11 Activation of a Non-Canonical Wnt Signalling Pathway Is Required for Cardiogenesis

Nature. 2002 Aug 8;418(6898):636-41. doi: 10.1038/nature00921.

Abstract

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.

MeSH terms

  • 3T3 Cells
  • Animals
  • Culture Media, Conditioned / pharmacology
  • Cytoskeletal Proteins / metabolism
  • Glycoproteins / metabolism*
  • 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
  • Protein Kinase C / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction* / drug effects
  • Stem Cells / drug effects
  • Stem Cells / enzymology
  • Stem Cells / metabolism
  • Trans-Activators / metabolism
  • Tumor Cells, Cultured
  • Wnt Proteins
  • Xenopus Proteins
  • Xenopus laevis / embryology*
  • beta Catenin

Substances

  • CTNNB1 protein, Xenopus
  • CTNNB1 protein, mouse
  • Culture Media, Conditioned
  • Cytoskeletal Proteins
  • Glycoproteins
  • RNA, Messenger
  • Trans-Activators
  • Wnt Proteins
  • Xenopus Proteins
  • beta Catenin
  • wnt11b protein, Xenopus
  • Protein Kinase C
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases