mortality/aging
• no pups are recovered at 7-10 days after birth while reduced numbers are seen at E14.5
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growth/size/body
• non-exencephalic E10.5 embryos are smaller
• E14.5 embryos are smaller
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microcephaly
(
J:235630
)
• non-exencephalic embryos are microcephalic
|
embryo
• E10.5 embryos are highly, but variably, dysmorphic
• non-exencephalic E10.5 embryos are less dysmorphic than exencephalic embyros
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• branchial arches are dysmorphic in non-exencephalic E10.5
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• all exencephalic and non-exencephalic embryos have hypoplastic first branchial arches
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• all exencephalic and non-exencephalic embryos have hypoplastic second branchial arches
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• non-exencephalic E10.5 embryos are smaller
• E14.5 embryos are smaller
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• in most exencephalic E10.5 embryos, neural tube closure is disrupted from the rhombencephalon forward and the spinal cord is spared
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nervous system
• fewer Ctip2-labeled cells across the ventrolateral to anteromedial extent indicating that cortical neurogenesis is slowed or diminished at E14.5
• at E14.5, basal, but not apical/radial, glial progenitors are compromised in the cortex
|
• proliferation of forebrain progenitors is disrupted at E10.5, with reduced numbers of Ki67+ and PH3+ cells, but no differences in BrdU+ cell numbers
• proliferation of cortical progenitors is disrupted
• reduction in basal-progenitor proliferation in the E14.5 cortex
• radial progenitors divide more slowly in the dorsal pallium at E10.5
|
• in most exencephalic E10.5 embryos, neural tube closure is disrupted from the rhombencephalon forward and the spinal cord is spared
|
• forebrain vesicle is shortened in the anterior-posterior axis in non-exencephalic E10.5
• however, neural crest is not significantly altered at E10.5, forebrain pattering is not significantly disrupted at E10.5 or E14.5, and neuroepithelial apical-basal polarity is maintained
|
• thickness of the cortical plate/intermediate zone is thinner in E14.5 cortex
• TuJ1-labeled early differentiating neurons are diminished in the cortical plate/intermediate zone of E14.5 embryos
• however, the thickness of the ventricular zone/subventricular zone is not reduced
|
• thickness of the cortical plate/intermediate zone is thinner in E14.5 cortex
• TuJ1-labeled early differentiating neurons are diminished in the cortical plate/intermediate zone of E14.5 embryos
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• E14.5 brain of non-exencephalic embryos is reduced in size
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• telencephalic structures, such as olfactory bulbs and ganglionic eminences, appear smaller in E14.5 non-exencephalic embryos
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• cortex is thinned in E14.5 non-exencephalic embryos
• cortical mantle in E14.5 non-exencephalic embryos is reduced 11-23% of wild-type, with the greatest reduction near the midpoint of the ventrolateral to dorsomedial axis
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• olfactory bulbs appear smaller in E14.5 non-exencephalic embryos
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• ganglionic eminences appear smaller in E14.5 non-exencephalic embryos
• subventricular zone basal progenitors are compromised
• exit of basal progenitor progeny from the subventricular zone is disrupted
|
exencephaly
(
J:235630
)
• 61-70% incidence of exencephaly, with about 60% of embryos exencephalic from E10.5 onwards
|
• E14.5 and E17.5 cortex shows reduced frequency of layer 2/3 projection neurons due to reduced basal-progenitor proliferation
• however, no change in frequency of layer 5/6 neurons is seen
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craniofacial
• branchial arches are dysmorphic in non-exencephalic E10.5
|
• all exencephalic and non-exencephalic embryos have hypoplastic first branchial arches
|
• all exencephalic and non-exencephalic embryos have hypoplastic second branchial arches
|
vision/eye
• microphthalmia or severe colobomas are present in 21/22 eyes of exencephalic embryos and 13/26 eyes of non-exencephalic embryos at E14.5
|
• eye position is shifted in E14.5 embryos
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• microphthalmia or severe colobomas are present in 21/22 eyes of exencephalic embryos and 13/26 eyes of non-exencephalic embryos at E14.5
|
cellular
• frequency of cyclin D nuclear labeling is reduced for basal progenitors, fewer BrdU+ Tbr2+ basal progenitors are seen in the subventricular zone, and a decrease in the number of PH3-labeled mitotic basal Tbr2+ basal progenitors, indicating that several phases of the cell cycle, especially M phase, are disrupted in basal, but not apical, E14.5 cortical progenitors
• however, there is no differences in the number of S-phase apical progenitors
|
• fewer Ctip2-labeled cells across the ventrolateral to anteromedial extent indicating that cortical neurogenesis is slowed or diminished at E14.5
• at E14.5, basal, but not apical/radial, glial progenitors are compromised in the cortex
|
• proliferation of forebrain progenitors is disrupted at E10.5, with reduced numbers of Ki67+ and PH3+ cells, but no differences in BrdU+ cell numbers
• proliferation of cortical progenitors is disrupted
• reduction in basal-progenitor proliferation in the E14.5 cortex
• radial progenitors divide more slowly in the dorsal pallium at E10.5
|