title: Atypical Protein Kinase C-Dependent Polarized Cell Division Is Required for Myocardial Trabeculation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Derek
authors.initials: D
authors.lastname: Passer
authors.affiliation: 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.
authors.forename: Annebel
authors.initials: A
authors.lastname: van de Vrugt
authors.affiliation: 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.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Atmanli
authors.affiliation: 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; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA. Electronic address: domian@mgh.harvard.edu.
authors.forename: Ibrahim J
authors.initials: IJ
authors.lastname: Domian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000235:genetics*; D016764:Cell Polarity; D004622:Embryo, Mammalian; D004699:Endocardium / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D038081:Organogenesis / Q000235:genetics*; D011485:Protein Binding; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure; D020107:Troponin T / Q000235:genetics / Q000378:metabolism; D000099293:Protein Kinase C-lambda
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000941:Antigens; D006657:Histones; D007527:Isoenzymes; D011493:Protein Kinase C; D020107:Troponin T; D000099293:Protein Kinase C-lambda; C518597:Par6 protein, mouse; C086178:pericentrin