β-Catenin and TCF Mediate Cell Positioning in the Intestinal Epithelium by Controlling the Expression of EphB/EphrinB

In the small intestine, the progeny of stem cells migrate in precise patterns. Absorptive, enteroendocrine, and goblet cells migrate toward the villus while Paneth cells occupy the bottom of the crypts. We show here that β-catenin and TCF inversely control the expression of the EphB2/EphB3 receptors...

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Bibliographic Details
Published in:	Cell Vol. 111; no. 2; pp. 251 - 263
Main Authors:	Batlle, Eduard, Henderson, Jeffrey T., Beghtel, Harry, van den Born, Maaike M.W., Sancho, Elena, Huls, Gerwin, Meeldijk, Jan, Robertson, Jennifer, van de Wetering, Marc, Pawson, Tony, Clevers, Hans
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 18-10-2002
Subjects:	Actins - physiology Animals Animals, Newborn Basic Helix-Loop-Helix Leucine Zipper Transcription Factors beta Catenin Cell Compartmentation Cell Differentiation Colorectal Neoplasms - metabolism Cytoskeletal Proteins - physiology Cytoskeleton - physiology DNA-Binding Proteins - physiology Ephrin-B1 - metabolism Ephrin-B2 - metabolism Gene Expression Regulation, Neoplastic Humans Intestinal Mucosa - cytology Intestinal Mucosa - metabolism Lymphoid Enhancer-Binding Factor 1 Mice Nerve Tissue Proteins Paneth Cells - cytology Receptors, Eph Family - genetics Receptors, Eph Family - metabolism Signal Transduction T Cell Transcription Factor 1 TCF Transcription Factors Trans-Activators - physiology Transcription Factor 4 Transcription Factor 7-Like 2 Protein Transcription Factors - physiology Tumor Cells, Cultured
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Summary:	In the small intestine, the progeny of stem cells migrate in precise patterns. Absorptive, enteroendocrine, and goblet cells migrate toward the villus while Paneth cells occupy the bottom of the crypts. We show here that β-catenin and TCF inversely control the expression of the EphB2/EphB3 receptors and their ligand ephrin-B1 in colorectal cancer and along the crypt-villus axis. Disruption of EphB2 and EphB3 genes reveals that their gene products restrict cell intermingling and allocate cell populations within the intestinal epithelium. In EphB2/ EphB3 null mice, the proliferative and differentiated populations intermingle. In adult EphB3 −/− mice, Paneth cells do not follow their downward migratory path, but scatter along crypt and villus. We conclude that in the intestinal epithelium β-catenin and TCF couple proliferation and differentiation to the sorting of cell populations through the EphB/ephrin-B system.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0092-8674 1097-4172
DOI:	10.1016/S0092-8674(02)01015-2