A model system is described for defining the physiologic functions of mammalian cadherins in vivo. 129/Sv embryonic stem (ES) cells, stably transfected with a dominant negative N-cadherin mutant (NCAD delta) under the control of a promoter that only functions in postmitotic enterocytes during their rapid, orderly, and continuous migration up small intestinal villi, were introduced into normal C57B1/6 (B6) blastocysts. In adult B6<->129/Sv chimeric mice, each villus receives the cellular output of several surrounding monoclonal crypts. A polyclonal villus located at the boundary of 129/Sv- and B6-derived intestinal epithelium contains vertical coherent bands of NCAD delta-producing enterocytes plus adjacent bands of normal B6-derived enterocytes. A comparison of the biological properties of these cell populations established that NCAD delta disrupts cell-cell and cell-matrix contacts, increases the rate of migration of enterocytes along the crypt-villus axis, results in a loss of their differentiated polarized phenotype, and produces precocious entry into a death program. These data indicate that enterocytic cadherins are critical cell survival factors that actively maintain intestinal epithelial function in vivo.
In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death.
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M L Hermiston, J I Gordon; In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death.. J Cell Biol 15 April 1995; 129 (2): 489–506. doi: https://doi.org/10.1083/jcb.129.2.489
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