Analysis Tools
nervous system
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• mice are born at Mendelian ratios and show no defects in neural tube closure
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• at E15.5, a higher fraction of neural progenitor cells (NPCs) have exited cell cycle in the cortex relative to controls (~60% versus ~40% BrdU+ Ki67- cells per total number of BrdU+ cells), indicating premature exhaustion of the progenitor pool; however, cleavage plane orientation of radial glial progenitors (RGPs) relative to the ventricular zone (VZ) surface is normal
• in culture, NPCs derived from E14.5 forebrains exhibit a higher rate of spontaneous neural differentiation, as shown by an increased fraction of Tuj1+ (neuronal) and GalC+ (oligodendrocytic) cells
• the multi-lineage differentiation potential of cultured NPCs is normal
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• at E15.5, the number of proliferating NPCs in the caudomedial cortex is reduced by ~30%, as shown by Ki67 or BrdU staining at the VZ
• at E15.5, the number of mitotic phosphorylated histone 3-labeled (pH3+) RGPs at the ventricular surface of the caudomedial cortex is reduced by 26% while the number of phosphorylated vimentin-labeled RGPs is reduced by 21.1%
• in culture, NPCs derived from E14.5 forebrains show a ~55% decrease in the proliferative index of Ki67+ Nestin+ progenitors as well as a significant reduction in Olig2+ progenitors
• however, no significant differences in apoptosis are noted in the caudomedial cortex at E12.5 or E15.5
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• at E15.5, the number of proliferating NPCs in the caudomedial cortex is reduced by ~30%, as shown by Ki67 or BrdU staining at the VZ
• at E15.5, the number of pH3+ RGPs at the ventricular surface of the caudomedial cortex is reduced by 26% while the number of phosphorylated
vimentin-labeled RGPs is reduced by 21.1%
• however, no defects are noted in the arrangement of apical cilia of VZ cells facing the ventricular lumen at E14.5
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• adult mice display underdevelopment of the rostral lobules with fusion of lobules 1-3, similar to Plxnb2tm1Matl homozygotes
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• at E15.5 and E17.5, lateral ventricles are often enlarged
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• adult brains display reduced size (thinning) of the corpus callosum
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• at P10, complete agenesis of the corpus callosum is often observed
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• at E15.5, cortical thickness and neuronal numbers are proportionally reduced in all layers, including germinal zones at the VZ/subventricular zone (SVZ) as well as distinct laminae in the cortical plate
• at E17.5, the number of early-born TBR1+ deep layer neurons is reduced by 34.6% in the caudomedial cortex; a similar reduction is noted in CTIP2+ deep layer cortical neurons
• at E17.5, the number of late-born SATB2+ upper layer neurons is reduced by 18.2%
• laminar organization of the cortex is normal at E17.5 and in adult mice
• no defects in lineage progression or overt radial or tangential migration defects are observed
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• cortical thinning begins at E12.5, becomes more obvious at E15.5 and E17.5, and is more severe in medial than lateral, and caudal than rostral cortical areas with a bias for the caudomedial cortex
• at E15.5, brains exhibit thinning of the medial cortex with a ~21% reduction in overall thickness
• adult brains show less thinning of the caudomedial cortex (~12% reduction)
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• adult mice display ectopias of granule cells in the molecular layer of caudal lobules, similar to Plxnb2tm1Matl homozygotes
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• at E15.5, the total number of SOX2+ neural progenitor cells in the caudomedial cortex is reduced by 19.2%
• at E15.5, the number of TBR2+ intermediate progenitor (IP) cells within the SVZ is reduced by 15%
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cellular
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• at E15.5, a higher fraction of neural progenitor cells (NPCs) have exited cell cycle in the cortex relative to controls (~60% versus ~40% BrdU+ Ki67- cells per total number of BrdU+ cells), indicating premature exhaustion of the progenitor pool; however, cleavage plane orientation of radial glial progenitors (RGPs) relative to the ventricular zone (VZ) surface is normal
• in culture, NPCs derived from E14.5 forebrains exhibit a higher rate of spontaneous neural differentiation, as shown by an increased fraction of Tuj1+ (neuronal) and GalC+ (oligodendrocytic) cells
• the multi-lineage differentiation potential of cultured NPCs is normal
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• at E15.5, the number of proliferating NPCs in the caudomedial cortex is reduced by ~30%, as shown by Ki67 or BrdU staining at the VZ
• at E15.5, the number of mitotic phosphorylated histone 3-labeled (pH3+) RGPs at the ventricular surface of the caudomedial cortex is reduced by 26% while the number of phosphorylated vimentin-labeled RGPs is reduced by 21.1%
• in culture, NPCs derived from E14.5 forebrains show a ~55% decrease in the proliferative index of Ki67+ Nestin+ progenitors as well as a significant reduction in Olig2+ progenitors
• however, no significant differences in apoptosis are noted in the caudomedial cortex at E12.5 or E15.5
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