Analysis Tools
mortality/aging
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• homozygous mutant mice die at E10.5
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nervous system
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• at E10.5, the neuroepithelium shows extra bending and lacks apically localized actin filaments and phosphorylated Myosin Light Chain 2 (P-Mlc2), which typically correlate with proper Rho-dependent cell constriction
• despite beta-catenin staining at the membranes, cell-cell junctions appear disorganized with less elongated cells and more rounded nuclei, suggesting defects in neuroepithelium polarization
• some cells are loosely separated from the neuroepithelium, indicating instability of cell-cell junctions
• integrin-mediated basement membrane assembly is highly disorganized, as indicated by weak expression of fibronectin and laminin, and mis-localized expression of keratin 8 (an epidermal layer marker)
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• in some areas, non-neuronal keratin 8 staining is detected in a thinner layer of neuroepithelium, unlike in wild-type controls where keratin 8 staining is only present in the developing epidermis
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• at E10.5, embryos exhibit consistent neural tube closure defects due to impaired apical constriction
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• neural tube fusion fails to occur at the hindbrain/cervical boundary
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• embryos show massive malformation of the developing brain
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• SEM shows a loosely organized pattern of cells in the hindbrain area
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embryo
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• at E10.5, the neuroepithelium shows extra bending and lacks apically localized actin filaments and phosphorylated Myosin Light Chain 2 (P-Mlc2), which typically correlate with proper Rho-dependent cell constriction
• despite beta-catenin staining at the membranes, cell-cell junctions appear disorganized with less elongated cells and more rounded nuclei, suggesting defects in neuroepithelium polarization
• some cells are loosely separated from the neuroepithelium, indicating instability of cell-cell junctions
• integrin-mediated basement membrane assembly is highly disorganized, as indicated by weak expression of fibronectin and laminin, and mis-localized expression of keratin 8 (an epidermal layer marker)
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• in some areas, non-neuronal keratin 8 staining is detected in a thinner layer of neuroepithelium, unlike in wild-type controls where keratin 8 staining is only present in the developing epidermis
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• at E10.5, embryos exhibit consistent neural tube closure defects due to impaired apical constriction
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• neural tube fusion fails to occur at the hindbrain/cervical boundary
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cellular
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• defects in neural tube closure are likely due to aberrations in active RhoA distribution, actin-myosin dynamics, and tension at cellcell adhesion
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• at E10.5, the neuroepithelium shows disorganization of integrin-mediated basement membrane assembly, as indicated by weak expression of the extracellular matrix components fibronectin and laminin
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