Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice
Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice
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DOI：
10.1074/jbc.c400352200
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Adelstein, RS
中科院分区：
文献类型：
--
作者：
Conti, MA;Even-Ram, S;Adelstein, RS
先前的工作已经表明，小鼠中非肌肉肌球蛋白重链II-B（NMHC II-B）的消融或突变导致心脏和大脑的缺陷，在胚胎第14.5天（E14.5）和出生之间发生死亡（Tullio，A.N.，Accili，D.，Ferrans，V.J.，Yu，Z.X.，武田，K.，Grinberg，A.，Westphal，H.，普雷斯顿，Y.A.，和Adelstein，R. S.等人（1997）Proc. Acad. Sci. U.S.A.94，12407-12412）。在这里，我们表明，小鼠消融NMHC II-A未能开发一个正常的模式胚胎与极化内脏内胚层的E6.5和死亡的E7.5。此外，在悬浮培养中生长的A（-）/A（-）胚状体不断脱落细胞。这些缺陷的细胞粘附和组织的组织被解释为损失的E-钙粘蛋白和β-连环蛋白本地化的细胞粘附网站在细胞培养和完整的胚胎。通过将针对NMHC II-A的siRNA引入野生型胚胎干细胞中，可以复制这些缺陷。我们的研究结果表明，一个单一的，具体的非肌肉肌球蛋白亚型在维持细胞间粘附在早期哺乳动物胚胎中的重要作用。
Previous work has shown that ablation or mutation of nonmuscle myosin heavy chain II-B (NMHC II-B) in mice results in defects in the heart and brain with death occurring between embryonic day 14.5 (E14.5) and birth (Tullio, A.N., Accili, D., Ferrans, V.J., Yu, Z.X., Takeda, K., Grinberg, A., Westphal, H., Preston, Y.A., and Adelstein, R. S. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 12407-12412). Here we show that mice ablated for NMHC II-A fail to develop a normal patterned embryo with a polarized visceral endoderm by E6.5 and die by E7.5. Moreover, A(-)/A(-) embryoid bodies grown in suspension culture constantly shed cells. These defects in cell adhesion and tissue organization are explained by loss of E-cadherin and beta-catenin localization to cell adhesion sites in both cell culture and in the intact embryos. The defects can be reproduced by introducing siRNA directed against NMHC II-A into wild-type embryonic stem cells. Our results suggest an essential role for a single, specific nonmuscle myosin isoform in maintaining cell-cell adhesions in the early mammalian embryo.