Vertebrate nonmuscle myosin IIs have been shown to play important roles in a variety of cellular processes such as cell motility, morphology, and cytokinesis, but the specific roles of the nonmuscle myosin II isoforms during embryonic development are still under study. 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. 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 A-/A- ES cells grown in culture and in the intact embryos. Localization of E-cadherin and Beta-catenin in B-/B- ES cells is similar to wild-type localization. Defects in the localization of the cell adhesion molecules can be reproduced by introducing siRNA directed against NMHC II-A into wild-type embryonic stem cells. These results suggest an essential role for a single nonmuscle myosin II isoform in maintaining cell-cell adhesions in the early mammalian embryo.
