Canonical Wnt signals are essential for homeostasis of the intestinal epithelium

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 appear...

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Bibliographic Details
Published in:Genes & development 2003-07, Vol.17 (14), p.1709-1713
Main Authors: Pinto, Daniel, Gregorieff, Alex, Begthel, Harry, Clevers, Hans
Format: Article
Language:English
Subjects:
Animals
beta Catenin
Cell Division - physiology
Cytoskeletal Proteins - metabolism
Homeostasis - physiology
Intercellular Signaling Peptides and Proteins
Intestinal Mucosa - metabolism
Mice
Mice, Transgenic
Proteins - metabolism
Proto-Oncogene Proteins - metabolism
Research Communications
Signal Transduction - physiology
Trans-Activators - metabolism
Wnt Proteins
Zebrafish Proteins
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.267103