Canonical Wnt signals are essential for homeostasis of the intestinal epithelium

Daniel Pinto, Alex Gregorieff, Harry Begthel, Hans Clevers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

840 Citaten (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.

Originele taal-2Engels
Pagina's (van-tot)1709-1713
Aantal pagina's5
TijdschriftGenes and Development
Nummer van het tijdschrift14
StatusGepubliceerd - 15 jul. 2003
Extern gepubliceerdJa


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