Analysis Tools
mortality/aging
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• embryos die around E16.5
(J:92081)
• embryos die between E14.5 and E16.5
(J:245570)
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cardiovascular system
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• livers exhibit sinusoidal dilatation at E14.5
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• E14.5 embryos show massive congestive failure in the liver with sinusoidal dilatation and focal hemorrhages
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• E14.5 hearts exhibit defects in outflow tract (OFT) alignment
• at E11.5, cardiac myocytes remain compact and do not invade the underlying cardiac cushions, indicating defective myocardialization of the developing OFT
• at E11.5, cardiac myocytes show abnormal enrichment of N-cadherin at the cell-cell boundaries, indicating defects in the disassembly of cell-cell adhesions
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• at E11.5, outflow tract (OFT) cardiac cushions are not invaded by cardiac myocytes, unlike in wild-type hearts
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• at E12.5, atrioventricular cushions have not fused and show no sign of elongation
• by E14.5, the superior and inferior cushions remain unfused and show no sign of maturation, indicating defects in fusion and remodeling
• at E12.5, TUNEL assays showed only ~1.1% of apoptotic mesenchymal cells in the unfused developing cushions relative to ~11.2% in wild-type cushions
• however, no changes in shape, size, and positioning of the cushions are found at E11.5 (prior to fusion)
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• atrioventricular cushions fail to remodel and acquire mature mitral and tricuspid valve leaflets by E14.5
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• at E14.5, all embryos exhibit double outlet right ventricle where both the aorta and the pulmonary artery emanate from the right ventricle
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• ~50% of E14.5 embryos develop ectopia cordis, with the heart protruding outside the thoracic chamber
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• in utero echocardiography showed a significant increase in left ventricular dimension in systole at E14.5
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• focal accumulation of blood cells in the liver at E14.5
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• in utero echocardiography showed a significant decrease in fractional shortening at E14.5
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• in utero echocardiography showed a significant decrease in heart rate at E14.5
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• E14.5 embryos exhibit congestive heart failure
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homeostasis/metabolism
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• E14.5 embryos develop generalized edema
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growth/size/body
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• palatal shelves are much shorter at E14.5
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cleft palate
(
J:245570
)
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• embryos exhibit cleft palates E14.5; the few embryos surviving to E16.5 still show cleft palates
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• at E14.5, palatal shelves are positioned vertically and flank the tongue with a large gap between them
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omphalocele
(
J:245570
)
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• all E14.5 embryos develop an omphalocele
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embryo
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• E14.5 embryos develop an umbilical hernia, indicating failure in ventral body wall closure
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craniofacial
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• palatal shelves are much shorter at E14.5
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cleft palate
(
J:245570
)
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• embryos exhibit cleft palates E14.5; the few embryos surviving to E16.5 still show cleft palates
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• at E14.5, palatal shelves are positioned vertically and flank the tongue with a large gap between them
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liver/biliary system
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• livers exhibit sinusoidal dilatation at E14.5
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• E14.5 embryos show massive congestive failure in the liver with sinusoidal dilatation and focal hemorrhages
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• focal accumulation of blood cells in the liver at E14.5
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• at E13.5, the liver is abnormally herniated outside the body
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muscle
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• in utero echocardiography showed a significant decrease in fractional shortening at E14.5
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• E13.5 embryos exhibit significantly more skeletal muscle cells in the ventral segments and significantly less skeletal muscle cells in the lateral segments of the diaphragm, rendering the lateral segments vulnerable to herniation
• however, lack of muscle cells in the lateral regions is not associated with increased apoptosis
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• abnormal diaphragm development leads to herniation of the liver into thoracic cavity
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skeleton
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• at E14.5, H&E staining showed only ~1.4 % of apoptotic mesenchymal cells with condensed and fragmented chromosomes in the middle of the fusing sternum relative to ~14.4% in wild-type sternums
• TUNEL assays failed to detect apoptotic cells near the midline, indicating impaired apoptosis in the fusing sternum
• only ~5.4% of mesenchymal cells stain positive for activated caspase-3 in the lower fusing sternum relative to ~46.2% in wild-type sternums
• however, no difference in p53 staining is observed
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• ~50% of E14.5 embryos exhibit a split lower sternum where the two halves are widely separated allowing the heart to protrude outside the thoracic chamber
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cellular
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• at E14.5, embryos show impaired apoptosis of mesenchymal cells in the fusing sternum
• at E12.5, mesenchymal cell apoptosis is impaired in the developing atrioventricular endocardial cushions which fail to fuse
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digestive/alimentary system
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• palatal shelves are much shorter at E14.5
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cleft palate
(
J:245570
)
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• embryos exhibit cleft palates E14.5; the few embryos surviving to E16.5 still show cleft palates
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• at E14.5, palatal shelves are positioned vertically and flank the tongue with a large gap between them
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