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

作者：Melissa Hirose Wong, Bonnee Rubinfeld, Jeffrey I. Gordon · 发表于：The Journal of Cell Biology · 年份：1998 · DOI：10.1083/jcb.141.3.765 · 被引用次数：182 · 研究领域：Wnt/β-catenin signaling in development and cancer、Cancer-related gene regulation、Kruppel-like factors research

beta-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 beta-catenin on proliferation, cell fate specification, adhesion, and migration in a mammalian epithelium, a human NH2-terminal truncation mutant (DeltaN89 beta-catenin) was expressed in the 129/Sv embryonic stem cell-derived component of the small intestine of adult C57Bl/6-ROSA26 left and right arrow 129/Sv chimeric mice. DeltaN89 beta-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. DeltaN89 beta-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 (DeltaN89 beta-catenin) intestinal epithelial cells and an accompanying slowing of cellular migration along crypt-villus units. 1-2% of 129/Sv (DeltaN89 beta-catenin) villi exhibited an abnormal branched architecture. Forced expression of DeltaN89 beta-catenin expression did not perturb the lev...