Analysis Tools
mortality/aging
| N |
• mice are reported to survive after birth (no postnatal stage provided)
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cardiovascular system
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• at E9.5, E10.5, and E11.5, atrioventricular (AV) cushions exhibit significantly lower numbers of mesenchymal cells than control cushions, suggesting disruption of endothelial to mesenchymal transition (EndMT)
• at E9.5, expression of AV cushion EndMT markers Snai1, Sox9, and Has2 is reduced in atrioventricular canals (AVCs), whereas Notch1 expression remains normal
• expression of Wnt4 in endocardium and of Bmp2 and its target Tbx2 in myocardium is reduced in AVCs at E9.5, whereas Tbx20 expression remains normal
• levels of phosphorylated-Smad1/5/8 (pSmad1/5/8) are significantly decreased in AV cushions at E10.5
• in vitro 3D collagen gel assays show that AVC explants from E9.5 embryos exhibit a significantly lower number of mesenchymal cells that migrate and invade into the matrix than control explants, indicating impaired EndMT
• addition of recombinant WNT4 or BMP2 protein partially rescues the EndMT defect, and inhibition of BMP2 with Noggin attenuates rescue of impaired EndMT by WNT4 protein, suggesting that Sox7 can regulate EndMT through Wnt4-Bmp2 signaling
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• at E9.5, E10.5, and E11.5, atrioventricular (AV) cushions exhibit significantly lower numbers of mesenchymal cells than control cushions
• at E9.5, AV cushions show significantly reduced glycosaminoglycans, indicating impaired extracellular matrix (ECM) formation
• hypocellular cushion phenotype is at least partly due to reduced endocardial cell proliferation: at E9.5, AV cushions show a sharp decrease in the number of KI67+ endocardial cells; the number of PCNA+ endocardial cells is much lower than that in control cushions
• KI67 staining shows reduced mesenchymal cell proliferation in AV cushions at E10.5
• however, no change in endocardial cell apoptosis is noted at E9.5, E11.5 and E14.5
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• at E14.5, 44.4% (4/9) of embryos show defects in closure of the atrial septum (ASD)
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• at E13.5, 63.6% (7/11) of embryos exhibit incomplete fusion or developmental delay of contact of the developing ventricular septum with the cardiac cushion versus 14.3% (1/7) of control embryos
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embryo
| N |
• embryos show no major changes in somite number at E9.5 and appear grossly normal at E10.5
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