Doctor of Philosophy (PhD)
Cellular & Integrative Physiology
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 (Grego-Bessa et al., 2007; Liu et al., 2010) and cardiac jelly (Camenisch et al., 2000) disrupt myocardial trabeculation, the role of cell polarity machinery in driving this process remains unclear. Herein, we demonstrate that atypical protein kinase C iota (Prkci) and its interacting partners of Par polarity complex are localized to the luminal side of luminal myocardial cells. Remarkably, a subset of these cells undergoes polarized cell division with the mitotic spindle and the cell division plane oriented perpendicular to the heart’s lumen and this polarization requires a normal composition of the cardiac jelly. Disruption of the polarity complex through cardiac specific deletion of Prkci or its downstream interacting partner NuMA, results in aberrant mitotic spindle alignment, loss of polarized cardiomyocyte division, and loss of normal myocardial trabeculation. Collectively these results layout a new mechanism for cardiac morphogenesis where in response to inductive signals, Prkci and its downstream partners direct polarized cell division of luminal myocardial cells to drive trabeculation in the early developing heart.
Passer, Derek L., "Atypical Protein Kinase C Dependent Polarized Cell Division is Required for Myocardial Trabeculation" (2015). Theses & Dissertations. 44.