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Letters to Nature

Nature 418, 636-641 (8 August 2002) | doi:10.1038/nature00921; Received 8 March 2002; Accepted 27 May 2002

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Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis

Petra Pandur1,2, Matthias Läsche1, Leonard M. Eisenberg3 & Michael Kühl1,2

  1. Abt Entwicklungsbiochemie, Junior group SFB 271, Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany
  2. Abt Biochemie, Universität Ulm, Albert-Einstein-Allee-11, D-89081 Ulm, Germany
  3. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA

Correspondence to: Michael Kühl1,2 Correspondence and requests for material should be addressed to M.K. (e-mail: Email: wnt_signaling@web.de).

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Formation of the vertebrate heart requires a complex interplay of several temporally regulated signalling cascades1. In Xenopus laevis, cardiac specification occurs during gastrulation and requires signals from the dorsal lip and underlying endoderm2. 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 development3, 4. 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.