Analysis Tools
mortality/aging
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• homozygous mutant embryos died at midgestation: no embryos survived past E11.5
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cardiovascular system
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• homozygous mutant embryos exhibited abnormal endothelial remodeling and poor vascular smooth muscle cell (VSMC) formation
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• most mutant embryos exhibited bilateral AVMs representing abnormal DA:CV fusions on both the left and right sides of the embryo; such AVMs occurred in multiple planes in the rostral trunk region
• in wild-type mice, VSMCs initially formed at the cranial-most aspect of the DA at E8.5 and surrounded the entire length of the DA by E9.5
• by E9-9.5, dorsal aorta and cardinal veins appear to be fused
• by E9.5, significantly endothelialtized tubes are observed between the anterior cardinal vein and DA at the level of the cardiac outflow tract; between the CV and DA at the midcardiac level; and between the CCV and DA below the heart
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• by E9.0, all homozygous mutant embryos displayed hyperdilation of the DA
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• most mutant embryos exhibited bilateral AVMs representing abnormal DA:CV fusions on both the left and right sides of the embryo; such AVMs occurred in multiple planes in the rostral trunk region
• hyperdilation of the common cardinal veins is observed at E9.0
• by E9-9.5, dorsal aorta and cardinal veins appear to be fused
• by E9.5, significantly endothelialtized tubes are observed between between the CV and DA at the midcardiac level; and between the CCV and DA below the heart
• beginning at E8.5, eight of ten homozygous mutant embryos developed arteriovenous malformations (AVM) involving arteriovenous shunts between the DA and cardinal veins (CV)
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• by E9.5, significantly endothelialtized tubes are observed between the anterior cardinal vein and DA at the level of the cardiac outflow tract
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• at E9.5, the vasculature of mutant yolk sacs resembled a meshwork of interconnected endothelial tubes
• in situ hybridization revealed that, Efnb2, an arterial-specific marker, was not detectable in mutant yolk sacs at E8.5 and E9.5, or in the caudal dorsal aortae (DA) of mutant embryos at E9.5; in addition, Efnb2 expression was downregulated, but not ablated, in mutant somitic and neural domains
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• in wild-type mice, VSMCs initially formed at the cranial-most aspect of the DA at E8.5 and surrounded the entire length of the DA by E9.5; in mutant embryos, VSMC formation was correctly initiated at E8.5, but became severely arrested by E9.5
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• arterial-venous shunting occurred during or immediately prior to axial turning
• by E9.0-E9.5, multiple arterial-venous shunts were evident throughout the mutant embryos
• beginning at E8.5, eight of ten homozygous mutant embryos developed arteriovenous malformations (AVM) involving arteriovenous shunts between the DA and cardinal veins (CV)
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• histology of mutant hearts revealed hypocellular cardiac cushions: the cushion cardiac jelly appeared acellular, despite normal formation of the endocardial layer
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• organ culture suggested that the hypoplastic heart defect may be secondary to the early AVMs and ensuing hemodynamic disruptions
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• by E9.5, significantly dilated endothelialized tubes were observed in the head; between the carotid artery and the primary head vein at the level of the mandibular arch; between the anterior cardinal vein and DA at the level of the cardiac outflow tract; between the CV and DA at the midcardiac level; and between the CCV and DA below the heart
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embryo
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• at E9.5, the vasculature of mutant yolk sacs resembled a meshwork of interconnected endothelial tubes
• in situ hybridization revealed that, Efnb2, an arterial-specific marker, was not detectable in mutant yolk sacs at E8.5 and E9.5, or in the caudal dorsal aortae (DA) of mutant embryos at E9.5; in addition, Efnb2 expression was downregulated, but not ablated, in mutant somitic and neural domains
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• mutant embryos appeared morphologically normal until E9.5; crown-rump length, somite number, as well as cardiac and neurological landmarks appeared normal before E9.0
• by E10.5, mutant embryos exhibited generalized developmental arrest
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• at E10.5, mutant yolk sacs lacked distinct vitelline vessels; injection of India ink indicated that vascular development was arrested at the primary capillary plexus stage
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hematopoietic system
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• in E10.0 wild-type embryos, hematopoietic clusters (HC) budded into the lumen from the intra-embryonic aortic endothelium, and were confined to the DA; in contrast, mutant embryos failed to restrict intravascular hematopoiesis to arteries, and displayed ectopic HC budding from the endothelium of the common cardinal vein as early as E8.5; by E10.0, clusters were also detected in mutant hyperdilated limb bud vessels
(J:65521)
• evidence supporting the ectopic development of intraembryonic HCs in cardinal veins, included the upregulation of the arterial marker CD43 in the subcardinal vein of mutant embryos
(J:85366)
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muscle
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• in wild-type mice, VSMCs initially formed at the cranial-most aspect of the DA at E8.5 and surrounded the entire length of the DA by E9.5; in mutant embryos, VSMC formation was correctly initiated at E8.5, but became severely arrested by E9.5
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• by E9.5, significantly dilated endothelialized tubes were observed in the head; between the carotid artery and the primary head vein at the level of the mandibular arch; between the anterior cardinal vein and DA at the level of the cardiac outflow tract; between the CV and DA at the midcardiac level; and between the CCV and DA below the heart
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