Poster Sessions

Dev-25

Xuefei Ma

X. Ma, R. S. Adelstein

The Role of Nonmuscle Myosin II-B in Mouse Heart Development

Mice ablated for nonmuscle myosin II-B die by E14.5 due to cardiac defects including a decrease in the number of cardiac myocytes and double outlet of the right ventricle (DORV). Here we report on the underlying mechanism for these defects. The decrease in cardiac myocytes has two causes: in NM II-B ablated (B-/B-) and in II-B hypomorphic mice a decrease in NM II-B results in defective cytokinesis. Interestingly the defects in cytokinesis (but not myocyte proliferation) can be rescued in vivo by a point mutant form of NM II-B (R709C in the myosin heavy chain, BC/BC mice) which has a compromised myosin MgATPase activity and cannot propel actin filaments in an in vitro. A second cause for decreased myocytes in both B-/B- and BC/BC hearts is due to defective development of the epicardium and impairment in epicardial FGF signaling. Both B-/B- and BC/BC mice develop a DORV, indicating that both the amount of NM II-B and its motor activity are essential for normal development of the cardiac outflow tract (OFT). This failure in myocardialization reflects the inability of BC/BC myocytes in the OFT to become polarized, disassemble their cell-cell adhesion complexes and migrate into the cardiac cushions.