In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death.
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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DOI：
10.1083/jcb.129.2.489
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发表时间：
1995-04
期刊：
影响因子：
--
通讯作者：
Gordon JI
中科院分区：
文献类型：
--
作者：
Hermiston ML;Gordon JI
描述了一种用于定义哺乳动物钙粘蛋白在体内的生理功能的模型系统。将129/Sv胚胎干（ES）细胞引入正常C57 B1/6（B6）囊胚中，所述ES细胞在启动子控制下用显性负性N-钙粘蛋白突变体（NCAD δ）稳定转染，所述启动子仅在有丝分裂后肠上皮细胞中在其快速、有序和连续迁移小肠绒毛期间起作用。在成年B6 <->129/Sv嵌合体小鼠中，每个绒毛接收周围几个单克隆隐窝的细胞输出。位于129/Sv-和B6-衍生的肠上皮的边界处的多克隆绒毛含有产生NCAD δ的肠细胞的垂直连贯条带加上正常B6-衍生的肠细胞的相邻条带。这些细胞群的生物学特性的比较确定NCAD δ破坏细胞-细胞和细胞-基质接触，增加肠上皮细胞沿着隐窝-绒毛轴的迁移速率，导致其分化的极化表型的丧失，并产生过早进入死亡程序。这些数据表明，肠细胞钙粘蛋白是关键的细胞存活因子，积极维持肠上皮功能在体内。
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.