Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza/CPZN 3200, 185 Cambridge Street, Boston, MA 02114-2790, USA; Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA; Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza/CPZN 3200, 185 Cambridge Street, Boston, MA 02114-2790, USA; Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
Cell Rep. 2016 Feb 23;14(7):1662-1672. doi: 10.1016/j.celrep.2016.01.030. Epub 2016 Feb 11.
A hallmark of cardiac development is the formation of myocardial trabeculations exclusively from the luminal surface of the primitive heart tube. Although a number of genetic defects in the endocardium and cardiac jelly disrupt myocardial trabeculation, the role of cell polarization remains unclear. Here, we demonstrate that atypical protein kinase C iota (Prkci) and its interacting partners are localized primarily to the luminal side of myocardial cells of early murine embryonic hearts. A subset of these cells undergoes polarized cell division with the cell division plane perpendicular to the heart's lumen. Disruption of the cell polarity complex by targeted gene mutations results in aberrant mitotic spindle alignment, loss of polarized cardiomyocyte division, and loss of normal myocardial trabeculation. Collectively, these results suggest that, in response to inductive signals, Prkci and its downstream partners direct polarized cell division of luminal myocardial cells to drive trabeculation in the nascent heart.
心脏发育的一个标志是，原始心管的管腔表面特异地形成心肌小梁。尽管心内膜和心胶质中的许多遗传缺陷会破坏心肌小梁的形成，但细胞极化的作用仍不清楚。在这里，我们证明非典型蛋白激酶 C iota（Prkci）及其相互作用的蛋白主要定位于早期鼠胚胎心脏心肌细胞的腔侧。这些细胞中的一部分经历着与心脏管腔垂直的极化细胞分裂。通过靶向基因突变破坏细胞极性复合物，会导致有丝分裂纺锤体排列异常、极化的心肌细胞分裂丧失以及正常心肌小梁丧失。总的来说，这些结果表明，Prkci 及其下游伙伴在感应信号后，指导腔侧心肌细胞的极化细胞分裂，以推动新生心脏中的小梁形成。
