mortality/aging
• most homozygotes are resorbed by E9.5
|
• 5% of homozygotes are resorbed at E7.5
|
• 9% of homozygotes are resorbed at E8.5
|
growth/size/body
• at E7.5, most homozygotes appear developmentally retarded and malformed relative to wild-type embryos
• at E9.5, surviving homozygotes are severely retarded
|
• at E7.5, malformed mutant embryos are half the size of wild-type embryos
• at E8.5 and E9.5, all surviving embryos are clearly smaller than wild-type embryos
|
• at E8.5, the anterior head mesenchyme underlying the neural folds is reduced and loosely packed
|
embryo
• homozygotes display defects in morphogenetic gastrulation movements
|
• homozygotes display impaired mesodermal cell migration out of the posterior primitve streak
• mesodermal patterning is aberrant, although mesoderm differentiates into diverse mesodermal subtypes, as cofirmed by marker analysis
|
• at E8.5, homozygotes lack somites and fail to elongate along the anterior-posterior axis
|
• at E7.5, most homozygotes appear developmentally retarded and malformed relative to wild-type embryos
• at E9.5, surviving homozygotes are severely retarded
|
• at E7.5, malformed mutant embryos are half the size of wild-type embryos
• at E8.5 and E9.5, all surviving embryos are clearly smaller than wild-type embryos
|
• at E7.5, malformed mutant embryos exhibit shorter egg cylinders
|
• at E8.5, the head process is thickened and expanded across the medial-lateral axis
|
• axial mesoderm is significantly expanded across the medial-lateral axis at the expense of paraxial mesoderm
|
• paraxial mesoderm is reduced
|
• at E9.5, 2 of 3 surviving homozygotes show small, disorganized headfolds
|
• at E8.5, the anterior head mesenchyme underlying the neural folds is reduced and loosely packed
|
• at E8.5, less severely affected homozygotes display smaller and disorganized neural folds
|
• at E8.5, homozygotes with disorganized neural folds show abnormally broad anterior midline structures that divide the neural plate in half
|
• at E9.5, one less severely affected homozygote shows a kinked, wiggly neural tube
|
• at E7.5, both epiblast and mesodermal cells accumulate in the streak region, resulting in a thickened and kinked primitve streak
• by E8.5, all surviving embryos show a large accumulation of cells in the posterior streak
• however, gastrulation and initial formation of the primitive streak is unaffected
|
• by E8.5, all surviving embryos show a large accumulation of cells in the posterior streak
|
• at E9.5, surviving homozygotes show absence or severe disorganization of the primitive streak
|
• by E8.5 and E9.5, all surviving mutant embryos lack somites
|
• at E8.5, homozygotes display an abnormal allantois with a large accumulation of cells at its base
|
• at E8.5, abnormal closure of the ectoplacental cavity results in chorion defects (swollen vesicles)
|
• "ruffled" endoderm layer at E8.5
|
• little extraembryonic mesoderm found under the endoderm at E8.5
|
• at E8.5, blood islands are reduced in number
|
• ruffled visceral yolk sac
|
nervous system
• at E8.5, homozygotes with disorganized neural folds show abnormally broad anterior midline structures that divide the neural plate in half
|
• at E9.5, one less severely affected homozygote shows a kinked, wiggly neural tube
|
• at E9.5, an ectopic midline bulge of cells is found in the ventral midbrain region
|
cardiovascular system
• at E8.5, less severely affected homozygotes display abnormal heart tubes
|