Canonical Wnt Signals Are Essential for Homeostasis of the Intestinal Epithelium

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2003 Jul 17

PMID 12865297

Citations 484

Authors

Daniel Pinto

Alex Gregorieff

Harry Begthel

Hans Clevers

Affiliations

Soon will be listed here.

Abstract

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 beta-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.

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