1. Epicardial Spindle Orientation Controls Cell Entry into the Myocardium
- Author
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Katherine Luby-Phelps, Ivy Lee, Mingfu Wu, Christopher L. Smith, Michelle D. Tallquist, and James A. Hall
- Subjects
Heart morphogenesis ,Beta-catenin ,Cell division ,Mice, Transgenic ,Nerve Tissue Proteins ,DEVBIO ,Spindle Apparatus ,Cell junction ,General Biochemistry, Genetics and Molecular Biology ,Article ,Adherens junction ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Movement ,Pregnancy ,Cell polarity ,Animals ,Molecular Biology ,beta Catenin ,030304 developmental biology ,Cell Proliferation ,Mice, Knockout ,0303 health sciences ,biology ,Myocardium ,Intracellular Signaling Peptides and Proteins ,Cell Polarity ,Membrane Proteins ,Heart ,Cell Biology ,Adherens Junctions ,Cell biology ,Spindle apparatus ,NUMB ,biology.protein ,Female ,CELLBIO ,Pericardium ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
SummaryDuring 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 β-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 β-catenin and Numb in the regulation of spindle orientation.
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