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 β-catenin, inhibition of c- myc expression, and subsequent up-regulation of p21 CIP1/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.

Keywords

Wnt signaling pathwayBiologyDKK1Intestinal epitheliumCell biologyEnterocyteHomeostasisEpitheliumTransgeneCell growthBeta-cateninLRP6Signal transductionEndocrinologyGeneticsGeneSmall intestine

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Year
2003
Type
article
Volume
17
Issue
14
Pages
1709-1713
Citations
1003
Access
Closed

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Daniel Pinto, Alex Gregorieff, Harry Begthel et al. (2003). Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes & Development , 17 (14) , 1709-1713. https://doi.org/10.1101/gad.267103

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DOI
10.1101/gad.267103