The Wnt/β-catenin pathway regulates cardiac valve formation

Adam F L Hurlstone, Anna Pavlina G Haramis, Erno Wienholds, Harry Begthel, Jeroen Korving, Fredericus Van Eeden, Edwin Cuppen, Danica Zivkovic, Ronald H A Plasterk, Hans Clevers

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Truncation of the tumour suppressor adenomatous polyposis coli (Apc) constitutively activates the Wnt/β-catenin signalling pathway. Apc has a role in development: for example, embryos of mice with truncated Apc do not complete gastrulation. To understand this role more fully, we examined the effect of truncated Apc on zebrafish development. Here we show that, in contrast to mice, zebrafish do complete gastrulation. However, mutant hearts fail to loop and form excessive endocardial cushions. Conversely, overexpression of Apc or Dickkopf 1 (Dkk1), a secreted Wnt inhibitor, blocks cushion formation. In wild-type hearts, nuclear β-catenin, the hallmark of activated canonical Wnt signalling, accumulates only in valve-forming cells, where it can activate a Tcf reporter. In mutant hearts, all cells display nuclear β-catenin and Tcf reporter activity, while valve markers are markedly upregulated. Concomitantly, proliferation and epithelial-mesenchymal transition, normally restricted to endocardial cushions, occur throughout the endocardium. Our findings identify a novel role for Wnt/β-catenin signalling in determining endocardial cell fate.
    Original languageEnglish
    Pages (from-to)633-637
    Number of pages4
    JournalNature
    Volume425
    Issue number6958
    DOIs
    Publication statusPublished - 9 Oct 2003

    Fingerprint

    Dive into the research topics of 'The Wnt/β-catenin pathway regulates cardiac valve formation'. Together they form a unique fingerprint.

    Cite this