JCB logo
amgmicro.com
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2884K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wong, M. H.
Right arrow Articles by Gordon, J. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wong, M. H.
Right arrow Articles by Gordon, J. I.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/1998//765 $5.00
The Journal of Cell Biology, Volume 141, Number 3, , 1998 765-777

Articles

Effects of Forced Expression of an NH2-terminal Truncated β-Catenin on Mouse Intestinal Epithelial Homeostasis



Melissa H. Wong*, Bonnee Rubinfeld{ddagger}, and Jeffrey I. Gordon*

* Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110; and {ddagger} Onyx Pharmaceuticals, Richmond, California 94806

β-Catenin functions as a downstream component of the Wnt/Wingless signal transduction pathway and as an effector of cell–cell adhesion through its association with cadherins. To explore the in vivo effects of β-catenin on proliferation, cell fate specification, adhesion, and migration in a mammalian epithelium, a human NH2-terminal truncation mutant ({Delta}N89β-catenin) was expressed in the 129/Sv embryonic stem cell–derived component of the small intestine of adult C57Bl/6–ROSA26{leftrightarrow} 129/Sv chimeric mice. {Delta}N89β-Catenin was chosen because mutants of this type are more stable than the wild-type protein, and phenocopy activation of the Wnt/Wingless signaling pathway in Xenopus and Drosophila. {Delta}N89β-Catenin had several effects. Cell division was stimulated fourfold in undifferentiated cells located in the proliferative compartment of the intestine (crypts of Lieberkühn). The proliferative response was not associated with any discernible changes in cell fate specification but was accompanied by a three- to fourfold increase in crypt apoptosis. There was a marked augmentation of E-cadherin at the adherens junctions and basolateral surfaces of 129/Sv ({Delta}N89β-catenin) intestinal epithelial cells and an accompanying slowing of cellular migration along crypt-villus units. 1–2% of 129/Sv ({Delta}N89β-catenin) villi exhibited an abnormal branched architecture. Forced expression of {Delta}N89β-catenin expression did not perturb the level or intracellular distribution of the tumor suppressor adenomatous polyposis coli (APC). The ability of {Delta}N89β-catenin to interact with normal cellular pools of APC and/or augmented pools of E-cadherin may have helped prevent the 129/Sv gut epithelium from undergoing neoplastic transformation during the 10-mo period that animals were studied. Together, these in vivo studies emphasize the importance of β-catenin in regulating normal adhesive and signaling functions within this epithelium.

Abbreviations used in this paper: β-gal, β-galactosidase; {Delta}N89β-catenin, NH2-terminal truncation mutant of human β-catenin lacking amino acid residues 1–89; APC, adenomatous polyposis coli protein or gene; BrdU, 5'-bromo-2'deoxyuridine; Cy3, indocarbocyanine; DBA, Dolichos biflorus agglutinin; ES cell, embryonic stem cell; Fabpl, fatty acid binding protein gene; GSK-3, glycogen synthase kinase-3; hGH, human growth hormone gene; LEF-1, lymphocyte enhancing factor-1; PLP, periodate-lysine-paraformaldehyde; RT, reverse transcriptase; TAg, T antigen; Tcf, T-cell factor; X-Gal, 5-bromo-4-chloro-3-indolyl β-D-galactoside.

Address all correspondence to Jeffrey I. Gordon, Department of Molecular Biology and Pharmacology, Box 8103, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110. Tel.: (314) 362-7243. Fax: (314) 362-7047. E-mail: jgordon{at}pharmdec.wustl.edu


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents