Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice.
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.
Conti
Mary Anne
MA
Laboratory of Molecular Cardiology, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA. contim@nhlbi.nih.gov
Even-Ram
Sharona
S
Liu
Chengyu
C
Yamada
Kenneth M
KM
Adelstein
Robert S
RS
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004707:Endoderm / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D018995:Myosin Heavy Chains / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D024507:Nonmuscle Myosin Type IIA / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D014781:Viscera / Q000196:embryology*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains