| Development of multi-cellular organisms requires the coordinate regulation of cellular proliferation, differentiation, migration, and death programs. The mouse intestinal epithelium represents an attractive model system for studying the control of these programs due to their rapid, continuous expression and spatial stratification along its crypt-villus axis. This thesis focuses on the development and application of a novel approach for studying intestinal epithelial biology in vivo. 129/Sv embryonic stem (ES) cells, stably transfected with a reporter of interest under the control of an intestine-specific promoter, are introduced into normal C57B1/6 (B6) blastocysts. In the resulting adult chimeric mice, each intestinal crypt is composed of a monoclonal population of cells descended from a multipotent stem cell. Each villus receives cells from several surrounding crypts. Polyclonal villi located at the borders of ES- and B6- derived epithelium are supplied by monoclonal B6 and 129/Sv crypts and can be used to define the biological consequences of reporter expression.;Chimeric-transgenic mice were used to study the physiologic functions of cadherins. E-cadherin is the principal intestinal epithelial cell cadherin. Expression of a dominant-negative N-cadherin (NCAD... |
