mortality/aging
• although present at normal Mendelian ratios between E8.5 and E10.5, all homozygotes appear severely compromised or dead by E10.5
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embryo
• at E9.5, the second heart field mesoderm lying dorsal to the heart shows both decreased cell proliferation and increased cell death relative to that in wild-type controls
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• at E9.5, mutant embryos exhibit multiple regions of abnormal apoptosis, as shown by TUNEL staining
• however, no apoptosis is detected in mutant heart tubes
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• at E8.5, all homozygotes display severely hypoplastic pharyngeal arches
• at E9.5, paucity of cells is noted in the pharyngeal mesoderm
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• at E9.5, the first pharyngeal arch is severely hypoplastic but appears vascularized
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• homozygotes display abnormal headfolds
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cardiovascular system
• at E9.5, the cardiac chamber opens directly into a dilated aortic sac
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• at E9.5, all homozygotes fail to form the cardiac outflow tract (OFT), unlike wild-type controls
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• at E9.5, the second heart field mesoderm lying dorsal to the heart shows both decreased cell proliferation and increased cell death relative to that in wild-type controls
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• at E9.5, all homozygotes exhibit unlooped hearts characterized by a primitive atrium caudal to a single ventricle, narrow inflow, and no obvious outflow tract, unlike wild-type controls
• at E8.5, only faint Fgf8 expression is noted within the pharyngeal mesoderm, reflecting both lower numbers of cardiac precursor cells and less chromagen present in the remaining cells
• at E9.0, homozygotes show loss of the second heart field (normally giving rise to RV and OFT formation) and reduced expression of several proliferative markers in the pharyngeal region
• at E9.5, the second heart field mesoderm lying dorsal to the heart shows both decreased cell proliferation and increased cell death
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• at E8.5 and E9.5, all homozygotes display an unlooped cardiac tube, unlike wild-type controls
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• at E9.5, homozygotes display a dilated heart tube with atrial chamber caudal to ventricle
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• at E9.5, all homozygotes fail to form the right ventricle (RV), unlike wild-type controls
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• at E9.5, mutant hearts exhibit only occasional proliferating cells, unlike wild-type hearts where nearly 10% of cardiomyocytes show anti-pHH3 staining
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cellular
• at E9.5, mutant hearts exhibit only occasional proliferating cells, unlike wild-type hearts where nearly 10% of cardiomyocytes show anti-pHH3 staining
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• at E9.5, mutant embryos exhibit multiple regions of abnormal apoptosis, as shown by TUNEL staining
• however, no apoptosis is detected in mutant heart tubes
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craniofacial
• at E8.5, all homozygotes display severely hypoplastic pharyngeal arches
• at E9.5, paucity of cells is noted in the pharyngeal mesoderm
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• at E9.5, the first pharyngeal arch is severely hypoplastic but appears vascularized
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muscle
• at E9.5, mutant hearts exhibit only occasional proliferating cells, unlike wild-type hearts where nearly 10% of cardiomyocytes show anti-pHH3 staining
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