First Author | Hermiston ML | Year | 1995 |
Journal | J Cell Biol | Volume | 129 |
Issue | 2 | Pages | 489-506 |
PubMed ID | 7721948 | Mgi Jnum | J:24411 |
Mgi Id | MGI:72177 | Doi | 10.1083/jcb.129.2.489 |
Citation | Hermiston ML, et al. (1995) 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 129(2):489-506 |
abstractText | 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. |