mortality/aging
|
|
• mice exhibit late embryonic lethality at E18.5
|
craniofacial
|
|
• at E17.5, mice exhibit severe craniofacial dysmorphism, including a secondary palatal cleft
• however, orofacial development is not affected prior to E11.5
|
|
|
• at E17.5, mice show complete loss or abrogated development of several cranial neural crest cell (CNC)-derived bones in the viscerocranium, anterior cranial vault, and prechordal skull base
• in contrast, mesoderm-derived skeletal elements of the posterior skull, including the parietal, intraparietal, petrous temporal, basioccipital, exoccipital and supraoccipital, are normal
|
|
|
• at E17.5, the presphenoid, alisphenoid, and orbitosphenoid were absent from the cranial base
|
|
|
• at E17.5, the basisphenoid of the cranial base shows impaired growth
|
|
|
• at E17.5, the medial portion of the frontal bones in the calvaria shows impaired growth
|
|
|
• slight frontal bossing at E17.5
|
|
|
• at E17.5, the alisphenoid is absent
|
|
|
• at E17.5, the orbitosphenoid is absent
|
|
|
• at E17.5, the presphenoid is absent
|
|
|
• at E17.5, the squamosal bone is absent
|
|
|
• reduction in cranial vault size at E17.5
|
|
|
• shallow orbits at E17.5
|
|
|
• at E17.5, the mandible is reduced in size
|
|
|
• at E17.5, the frontal process of the maxilla is reduced in size
|
|
|
• at E17.5, the palatine bones of the maxilla are absent
|
|
|
• at E17.5, the vomer is reduced in size
|
|
|
• at E17.5, the jugal (zygoma) bone is absent
|
|
|
• at E11.5, apoptotic (ApopTag+) cells are detected throughout the orofacial region, esp. in the developing palatal areas
• however, ApopTag+ cells are not observed in the palatal region at E17.5
|
|
|
• at E17.5, the presumptive secondary palate shows only limited mesenchymal condensation and a complete absence of mineralization in the truncated palatal shelves
• secondary palate development is arrested prior to mineralization around E13.5, with a significant increase in the expression levels of apoptotic markers Caspase 3 and Trp53 in palatal tissue esp. at E13.5
• expression levels for senescence marker Cdkn1a (p21) are increased at E11.5 and E13.5
• however, primary palate development and the initial stages of secondary palate formation appear unaffected
|
|
|
• at E16.5, palatal shelves exhibit arrested growth, remaining vertically oriented in position and are morphologically similar to the shelves of an E13.5 wild-type embryo
|
|
|
• at E16.5, intramembranous ossification is completely absent in the palatal shelf region
• in contrast, the nasal septal cartilage, which develops from the Pax2-Cre-negative frontonasal region, is present
|
|
|
• at E16.5, palatal shelves remain vertically oriented in position
|
|
|
• at ~E13.5, palatal shelves are vertically positioned along the side of the tongue but show a slight reduction in size
|
|
|
• midface hypoplasia at E17.5
|
|
|
• complete cleft of the secondary palate at E16.5 and E17.5
|
growth/size/body
|
|
• slight frontal bossing at E17.5
|
|
|
• at E17.5, the presumptive secondary palate shows only limited mesenchymal condensation and a complete absence of mineralization in the truncated palatal shelves
• secondary palate development is arrested prior to mineralization around E13.5, with a significant increase in the expression levels of apoptotic markers Caspase 3 and Trp53 in palatal tissue esp. at E13.5
• expression levels for senescence marker Cdkn1a (p21) are increased at E11.5 and E13.5
• however, primary palate development and the initial stages of secondary palate formation appear unaffected
|
|
|
• at E16.5, palatal shelves exhibit arrested growth, remaining vertically oriented in position and are morphologically similar to the shelves of an E13.5 wild-type embryo
|
|
|
• at E16.5, intramembranous ossification is completely absent in the palatal shelf region
• in contrast, the nasal septal cartilage, which develops from the Pax2-Cre-negative frontonasal region, is present
|
|
|
• at E16.5, palatal shelves remain vertically oriented in position
|
|
|
• at ~E13.5, palatal shelves are vertically positioned along the side of the tongue but show a slight reduction in size
|
|
|
• midface hypoplasia at E17.5
|
|
|
• complete cleft of the secondary palate at E16.5 and E17.5
|
digestive/alimentary system
|
|
• at E17.5, the presumptive secondary palate shows only limited mesenchymal condensation and a complete absence of mineralization in the truncated palatal shelves
• secondary palate development is arrested prior to mineralization around E13.5, with a significant increase in the expression levels of apoptotic markers Caspase 3 and Trp53 in palatal tissue esp. at E13.5
• expression levels for senescence marker Cdkn1a (p21) are increased at E11.5 and E13.5
• however, primary palate development and the initial stages of secondary palate formation appear unaffected
|
|
|
• at E16.5, palatal shelves exhibit arrested growth, remaining vertically oriented in position and are morphologically similar to the shelves of an E13.5 wild-type embryo
|
|
|
• at E16.5, intramembranous ossification is completely absent in the palatal shelf region
• in contrast, the nasal septal cartilage, which develops from the Pax2-Cre-negative frontonasal region, is present
|
|
|
• at E16.5, palatal shelves remain vertically oriented in position
|
|
|
• at ~E13.5, palatal shelves are vertically positioned along the side of the tongue but show a slight reduction in size
|
|
|
• complete cleft of the secondary palate at E16.5 and E17.5
|
skeleton
|
|
• at E17.5, mice show complete loss or abrogated development of several cranial neural crest cell (CNC)-derived bones in the viscerocranium, anterior cranial vault, and prechordal skull base
• in contrast, mesoderm-derived skeletal elements of the posterior skull, including the parietal, intraparietal, petrous temporal, basioccipital, exoccipital and supraoccipital, are normal
|
|
|
• at E17.5, the presphenoid, alisphenoid, and orbitosphenoid were absent from the cranial base
|
|
|
• at E17.5, the basisphenoid of the cranial base shows impaired growth
|
|
|
• at E17.5, the medial portion of the frontal bones in the calvaria shows impaired growth
|
|
|
• slight frontal bossing at E17.5
|
|
|
• at E17.5, the alisphenoid is absent
|
|
|
• at E17.5, the orbitosphenoid is absent
|
|
|
• at E17.5, the presphenoid is absent
|
|
|
• at E17.5, the squamosal bone is absent
|
|
|
• reduction in cranial vault size at E17.5
|
|
|
• shallow orbits at E17.5
|
|
|
• at E17.5, the mandible is reduced in size
|
|
|
• at E17.5, the frontal process of the maxilla is reduced in size
|
|
|
• at E17.5, the palatine bones of the maxilla are absent
|
|
|
• at E17.5, the vomer is reduced in size
|
|
|
• at E17.5, the jugal (zygoma) bone is absent
|
vision/eye
|
|
• at E17.5, the orbitosphenoid is absent
|
|
|
• shallow orbits at E17.5
|
|
|
• exophthalmos due to shallow orbits at E17.5
|
|
|
• absence of eyelid formation at E17.5
|
nervous system
|
|
• slight cerebral hemorrhage at E17.5
|
hearing/vestibular/ear
|
|
• at E17.5, the tympanic ring is reduced in size
|
cellular
|
|
• at E11.5, the total number of EdU+ cells are markedly reduced in the region of the developing brain and first pharyngeal arch
|
cardiovascular system
|
|
• slight cerebral hemorrhage at E17.5
|
Analysis Tools