mortality/aging
• all die between E7.5 and E8.5
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embryo
• increase in apoptotic cells in the distal epiblast and visceral endoderm
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• data suggest that anterior to posterior cell movement does not occur in the proximal epiblast
• at E6.5, in the distal visceral endoderm cells positive for Hek, Dkk1, and Nodal fail to migrate toward the anterior
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• arrest between E6.0 and E6.5
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• the Wnt3 and T expression domains are expanded anteriorly
• nuclei in the epiblast are more spherical rather than ellipsoid and elongated as in controls
• the epiblast is disorganized with ectopic mitotic cells
• expression analysis indicates that apical-basal cell polarity is disrupted
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• at E6.5, in the distal visceral endoderm cells positive for Hek, Dkk1, and Nodal fail to migrate toward the anterior
• at E7.5 Lefty1+ cells are dispersed rather than migrating as a cohort
• the visceral endoderm fails to form squamous cells in the distal egg cylinder
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cellular
• many mitotic spindles are oriented obliquely or parallel rather than perpendicular
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• on the apical side of the epiblast
• however, the overall mitotic index is only slightly lower than in controls
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• increase in apoptotic cells in the distal epiblast and visceral endoderm
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• data suggest that anterior to posterior cell movement does not occur in the proximal epiblast
• at E6.5, in the distal visceral endoderm cells positive for Hek, Dkk1, and Nodal fail to migrate toward the anterior
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