mortality/aging
• embryos die at E9.5-10
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embryo
• at E9 and 9.5 vasculature of placenta disintegrates
• embryonic endothelial cells invade the chorion but fail to penetrate the trophoblast layer and do not establish close interactions with maternal sinuses
• placentas of mutants fail to develop past E8.75, contain only spongiotrophoblast but not labyrinth zone and remain much thinner than wild-type
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• endothelial cells form channels that begin to disconnect from each other at their branches
• at E9 and 9.5 vasculature of yolk sac disintegrates
• at E9.5 endothelial cells disappear in vitelline vessels
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• embryos do not progress beyond E8.75-9 developmental stage
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• at E9, mutants have fewer somites than wild-type embryos
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cardiovascular system
• sprouting of intersomitic vessels is impaired
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• at E9 and 9.5 vasculature of placenta disintegrates
• embryonic endothelial cells invade the chorion but fail to penetrate the trophoblast layer and do not establish close interactions with maternal sinuses
• placentas of mutants fail to develop past E8.75, contain only spongiotrophoblast but not labyrinth zone and remain much thinner than wild-type
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• endocardial cells detach from each other and are scattered in ventricular cavity
• beyond E8.75-9, endothelial cells throughout the vasculature progressively become disconnected from each other and exhibit gaps, detach from their basement membrane, and become scattered inside lumen
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• remodeling of intersomitic vessels into network of large and small branches is impaired in embryos
• vasculature at E9 and 9.25 disintegrates
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• at E9.5 cephalic vessels are dilated
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• by E8.5, some blood vessels (thoracic dorsal aorta, anterior cardinal vein) in mutants have a minimal or no lumen while others are dilated (cephalic vessels)
• sprouting of intersomitic vessels is impaired
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• endothelial cells form channels that begin to disconnect from each other at their branches
• at E9 and 9.5 vasculature of yolk sac disintegrates
• at E9.5 endothelial cells disappear in vitelline vessels
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• scattered disconnected endocardial cells and a loosely assembled myocardium that is detached lie scattered in center of outflow tract and occlude the ventricular lumen at E8.75
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• looping is initiated normally but development is retarded by E9.5
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craniofacial
hematopoietic system
N |
• hematopoiesis is not significantly impaired in mutants
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cellular
• endothelial cells in mutants show impaired survival and elevated apoptosis relative to wild-type cells in vivo and in culture
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