mortality/aging
• of those alive at E14.5 none survive to birth
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• some die before E14.5
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embryo
• abnormalities in the primitive streak, node, and anterior visceral endoderm suggest that axial rotation is abnormal
• 20% of embryos develop with the anterior region outside the yolk sac (type II) and 29% of embryos develop completely outside the yolk sac (type III), the remainder develop within the yolk sac (type I)
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• expression analysis indicates abnormal cell positions along the anterior posterior axis at E7.5
• defects in axial patterning become more pronounced by E8.5
• severe defects in anterior patterning are seen in all 3 types of embryos
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• some embryos arrest prior to gastrulation
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• at E8.5 type III embryos lack any apparent lateral plate mesoderm
• at E8.5 type I embryos lack normal asymmetric gene expression in the left lateral plate mesoderm
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• type I embryos lack the normal ventral midline separation of the neural folds at E8.5
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• in type II embryos the head neuroectoderm is disorganized with repeated foldings
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• type II embryos lack a distinct floor plate in the trunk region
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• in some type II embryos
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• in some type II embryos the notochord is present in the trunk but ends abruptly at the level of the head
• in type III embryos the notochord end short of the most anterior region
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• type I embryos lack a prechordal plate in the forebrain region at E8.5
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• in type II and type III embryos
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• expression analysis at E7.5 indicates truncation of the primitive streak
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• at E7.5, the node appears to be more proximal in location compared to controls
• at E8.5 in type II embryos Nodal expressing cells are found across the midline rather than confined to the periphery as in controls
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• at E8.5 type III embryos lack a recognizable node
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fused somites
(
J:73506
)
• all type II embryos show fusion of somites across the midline
• some type III embryos have fused somites
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• a constriction is present at the boundary
• the lateral edges of the mesodermal wings encroach on the anterior midline at the site where the anterior visceral endoderm normally contacts the underlying anterior embryonic ectoderm
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• in distal locations cells with cuboidal shapes are present where in controls the cell are squamous in shape
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nervous system
• in type II embryos the head neuroectoderm is disorganized with repeated foldings
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• type II embryos lack a distinct floor plate in the trunk region
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• type II and type III embryos lack demarcations between fore-, mid- and hindbrain regions
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• seen in type I embryos at E14.5
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digestive/alimentary system
• in a few type I embryos at E14.5 the stomach is located on the right side or shows incomplete rotation
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• expression analysis suggests that type III embryos lack gut endoderm and there is no morphologically recognizable gut tube in these embryos
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• in type II embryos no recognizable foregut pocket is found
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• in type I embryos the foregut does not extend as far anteriorly as in controls
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• abnormally narrow and prematurely closed in type II embryos
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cardiovascular system
• randomized direction of looping in type I embryos
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• type II and type III embryos fail to develop a heart tube
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• in all type I embryos at E14.5
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respiratory system
• in most type I embryos at E14.5
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liver/biliary system
small liver
(
J:73506
)
• in some type I embryos at E14.5 the liver is reduced in size and/or pale
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pale liver
(
J:73506
)
• in some type I embryos at E14.5 the liver is reduced in size and/or pale
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growth/size/body
• type II and type III embryos have a ventral orientation of the head
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• in most type I embryos at E14.5
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