Analysis Tools
mortality/aging
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• homozygotes die between E10.5 and E11.5
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embryo
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• at E10.5, pharyngeal arches appear grossly normal but smaller in size
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• at E10.5, mutant embryos are noticeably smaller than wild-type or heterozygous controls
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• at E10.5, mutant embryos display reduced mesenchymal cell density and many gaps between cells
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• at E10.5, the neuroepithelium in the neural tube displays reduced cell density and many gaps between cells
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• at E10.5, ~10% of mutant embryos exhibit an open neural tube at the midbrain and forebrain
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• at E10.5, somites with a partially collapsed appearance are observed
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• at E10.5, mutant embryonic extracts display hyperactivation of three major MAP kinase pathways (ERK1/2, JNK, p38) as well as AKT signaling
• however, no change in the activation of TGF-beta signaling associated with Smad2 phosphorylation is observed
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• at E10.5, mutant embryos have a paler yolk sac than controls
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nervous system
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• at E10.5, ~10% of mutant embryos exhibit intracranial hemorrhages
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• at E10.5, TUNEL staining in midbrain neuroepithelium shows a 7-fold increase in apoptosis relative to wild-type controls
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• at E10.5, immunofluorescence staining of class III beta-tubulin (a marker of postmitotic neurons) in the hindbrain neuroepithelium indicates a reduced number of differentiated neurons relative to wild-type controls
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• at E10.5, the neuroepithelium in the neural tube displays reduced cell density and many gaps between cells
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• at E10.5, ~10% of mutant embryos exhibit an open neural tube at the midbrain and forebrain
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• at E10.5, ~10% of mutant embryos lack the telencephalic vesicles
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• at E10.5, ~10% of mutant embryos exhibit collapsed midbrain regions
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• at E10.5, ~10% of mutant embryos exhibit collapsed hindbrain regions
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• at E10.5, dorsal root ganglia appear misorganized and display a lower cell density
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• at E10.5, the percentage of BrdU-positive cells in the neuroepithelium is only ~20% relative to ~50% in wild-type controls
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cardiovascular system
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• at E10.5, trabeculae appear underdeveloped
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• at E10.5, the myocardium is abnormally thin (only 1-3 cells thick)
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• at E10.5, some heart structures appear to be less developmentally advanced and/or abnormal
• however, normal looping and formation of a four-chambered heart is observed
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• at E10.5, ~10% of mutant embryos exhibit intracranial hemorrhages
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craniofacial
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• at E10.5, ~10% of mutant embryos display severe defects in craniofacial development
• however, frontonasal process formation appears normal
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• at E10.5, pharyngeal arches appear grossly normal but smaller in size
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muscle
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• at E10.5, trabeculae appear underdeveloped
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• at E10.5, the myocardium is abnormally thin (only 1-3 cells thick)
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vision/eye
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• at E10.5, retina development is grossly normal although the density of neuroepithelial cells appears to be reduced
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hematopoietic system
growth/size/body
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• at E10.5, mutant embryos are noticeably smaller than wild-type or heterozygous controls
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cellular
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• at E10.5, TUNEL staining in midbrain neuroepithelium shows a 7-fold increase in apoptosis relative to wild-type controls
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• at E10.5, immunofluorescence staining of class III beta-tubulin (a marker of postmitotic neurons) in the hindbrain neuroepithelium indicates a reduced number of differentiated neurons relative to wild-type controls
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