Analysis Tools
cardiovascular system
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• at E10.5, outflow tract (OFT) membrane cells are disorganized with loss of beta-catenin localization at the adherens junctions
• both disorganization and loss of polarity are noted within the OFT, consistent with other planar cell polarity (PCP) loss-of-function models
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• at E14.5, nineteen of 30 embryos (63%) exhibit cardiac defects, only seen in 1 of 24 (4%) wild-type controls
• observed congenital heart defects are characteristic of PCP disruption
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• at E14.5, embryos show ventricular thinning in the left ventricular (LV) compact myocardium
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• whole hearts from E12.5 embryos show evidence of PCP gene expression dysregulation, with significant decreases in Daam1, Jnk, and Rhoa
• whole heart lysates from E12.5 embryos show marked reductions in PCP proteins and terminal PCP components including phosphorylated MYPT1, phosphorylated MLC (pMLC), and phosphorylated DVL2 (pDVL2)
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• at E14.5, embryos show evidence of cellular movement defects, including reduced lamellipodia and filopodia within the OFT cushion
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• at E11.5, left ventricular (LV) wall cardiomyocytes are disorganized and less compact with more space between cells and without evident SCRIB at the basolateral membrane of the ventricular epicardium, indicating cardiomyocyte disorganization and disrupted polarity
• at E14.5, septal cardiomyocytes appear rounded, lack lamellipodia and filopodia, and fail to achieve septal closure with an evident membranous VSD
• at E14.5, LV wall cardiomyocyte size (measured as total area) is normal but cardiomyocyte roundness and disorganization (measured as lacunarity or the average space between cells) are significantly increased
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• at E14.5, four of 21 embryos (19%) exhibit double outlet right ventricle (DORV)
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• at E14.5, one of 22 embryos displays a double inlet left ventricle, with both the left atrium and mitral valve and right atrium and tricuspid valve emptying into the left ventricle
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• at E14.5, thirteen of 27 embryos (48%) exhibit ventricular septal defects (VSDs), including membranous VSDs and muscular VSDs
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• at E14.5, left ventricular (LV) walls are 36% thinner than in wild-type hearts
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• at E14.5, hearts show increased left ventricular (LV) cardiomyocyte proliferation localized to the ventricular trabeculae
• however, cardiomyocyte proliferation within the LV wall and ventricular septum is normal, and no significant decrease in cardiomyocyte apoptosis is noted at E14.5
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cellular
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• at E14.5, hearts show increased left ventricular (LV) cardiomyocyte proliferation localized to the ventricular trabeculae
• however, cardiomyocyte proliferation within the LV wall and ventricular septum is normal, and no significant decrease in cardiomyocyte apoptosis is noted at E14.5
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• following stimulation with PCP ligand WNT5a, mouse embryonic fibroblasts (MEFs) show significantly reduced activated myosin light chain phosphatase (MYPT1) relative to wild-type MEFs, indicating disrupted PCP signaling pathway activation in cultured cells
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muscle
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• at E14.5, embryos show ventricular thinning in the left ventricular (LV) compact myocardium
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• at E14.5, hearts show increased left ventricular (LV) cardiomyocyte proliferation localized to the ventricular trabeculae
• however, cardiomyocyte proliferation within the LV wall and ventricular septum is normal, and no significant decrease in cardiomyocyte apoptosis is noted at E14.5
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