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PMID: 17785439 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells.

Molecular and cellular biology ·Vol. 27 ·No. 21 ·2007-11-00 ·Pages 7551-9

Fevr T, Robine S, Louvard D, Huelsken J

Abstract

The Wnt signaling pathway is deregulated in over 90% of human colorectal cancers. beta-Catenin, the central signal transducer of the Wnt pathway, can directly modulate gene expression by interacting with transcription factors of the TCF/LEF family. In the present study we investigate the role of Wnt signaling in the homeostasis of intestinal epithelium by using tissue-specific, inducible beta-catenin gene ablation in adult mice. Block of Wnt/beta-catenin signaling resulted in rapid loss of transient-amplifying cells and crypt structures. Importantly, intestinal stem cells were induced to terminally differentiate upon deletion of beta-catenin, resulting in a complete block of intestinal homeostasis and fatal loss of intestinal function. Transcriptional profiling of mutant crypt mRNA isolated by laser capture microdissection confirmed those observations and allowed us to identify genes potentially responsible for the functional preservation of intestinal stem cells. Our data demonstrate an essential requirement of Wnt/beta-catenin signaling for the maintenance of the intestinal epithelium in the adult organism. This challenges attempts to target aberrant Wnt signaling as a new therapeutic strategy to treat colorectal cancer.

MeSH Terms
Animals Biomarkers/metabolism Cell Death Cell Differentiation Cell Lineage Cell Proliferation Down-Regulation Homeostasis Intestinal Mucosa/cytology,metabolism,ultrastructure Intestines/cytology,physiology,ultrastructure Mice Mice, Mutant Strains Signal Transduction Stem Cells/cytology,metabolism Transcription, Genetic Wnt Proteins/metabolism beta Catenin/deficiency,metabolism
Chemicals
Biomarkers Wnt Proteins beta Catenin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fevr Tea
Ecole Polytechnique Fédérale de Lausanne, ISREC (Swiss Institute for Experimental Cancer Research), Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Robine Sylvie
Louvard Daniel
Huelsken Joerg
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.01034-07
Published
2007-11-00
Epub
2007-00-04
Pages
7551-9
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2169070
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.01034-07 PMC Full Text View journal details
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