Epicardial spindle orientation controls cell entry into the myocardium.
During heart morphogenesis, epicardial cells undergo an epithelial-to-mesenchymal transition (EMT) and migrate into the subepicardium. The cellular signals controlling this process are poorly understood. Here, we show that epicardial cells exhibit two distinct mitotic spindle orientations, directed either parallel or perpendicular to the basement membrane. Cells undergoing perpendicular cell division subsequently enter the myocardium. We found that loss of beta-catenin led to a disruption of adherens junctions and a randomization of mitotic spindle orientation. Loss of adherens junctions also disrupted Numb localization within epicardial cells, and disruption of Numb and Numblike expression in the epicardium led to randomized mitotic spindle orientations. Taken together, these data suggest that directed mitotic spindle orientation contributes to epicardial EMT and implicate a junctional complex of beta-catenin and Numb in the regulation of spindle orientation.
Wu
Mingfu
M
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Smith
Christopher L
CL
Hall
James A
JA
Lee
Ivy
I
Luby-Phelps
Kate
K
Tallquist
Michelle D
MD
D022005:Adherens Junctions / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D006321:Heart / Q000196:embryology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010496:Pericardium / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure*; D051176:beta Catenin / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; C106292:Numbl protein, mouse; D051176:beta Catenin