Canonical Wnt signals are essential for homeostasis of the intestinal epithelium

Daniel Pinto, Alex Gregorieff, Harry Begthel, Hans Clevers

Research output: Contribution to journalArticlepeer-review

387 Citations (Scopus)


To assess the critical role of Wnt signals in intestinal crypts, we generated transgenic mice ectopically expressing Dickkopf1 (Dkk1), a secreted Wnt inhibitor. We find that epithelial proliferation is greatly reduced coincidentally with the loss of crypts. Although enterocyte differentiation appears unaffected, secretory cell lineages are largely absent. Disrupted intestinal homeostasis is reflected by an absence of nuclear β-catenin, inhibition of c-myc expression, and subsequent up-regulation of p21CIP1/WAF1. Thus, our data are the first to establish a direct requirement for Wnt ligands in driving proliferation in the intestinal epithelium, and also define an unexpected role for Wnts in controlling secretory cell differentiation.

Original languageEnglish
Pages (from-to)1709-1713
Number of pages5
JournalGenes and Development
Issue number14
Publication statusPublished - 15 Jul 2003
Externally publishedYes


  • Canonical Wnt signaling
  • Dickkopf1
  • Intestinal epithelium


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