mortality/aging
behavior/neurological
• at P0, mice exhibit difficulty in feeding
|
respiratory system
• at P0, nasal cartilage is hypoplastic or absent
|
• at P0, mice exhibit difficulty in breathing
|
craniofacial
• by E14.5, severe craniofacial defects, including micrognathia and glossoptosis, are observed
• however, embryos appear morphologically normal until E12.5
|
• at P0, mice exhibit defects in bone development in the skull
|
• at E12.5, Meckels cartilage development is delayed
• at E14.5, Meckels cartilage appears to be loosely organized/packed
• at E12.5 and E14.5, Sox9 is upregulated in Meckels cartilage as well as in the mesenchyme surrounding Meckels cartilage
|
• by E14.5, Meckels cartilage is severely hypoplastic
|
• at P0, mice exhibit defects in cartilage development in the skull
|
• at P0, the frontal bone is underdeveloped
|
• at P0, the temporal bone is underdeveloped; otic bones are hypoplastic
|
• lower incisors are markedly smaller at E17.5
|
• at E17.5, upper incisors are developmentally delayed, having only reached the bell stage, whereas control upper incisors are transitioning from the late bell to eruption stage
• at P0, incisors are underdeveloped
|
• upper and lower molars are developmentally delayed at the bud stage at E14.5 and early bell stage at E17.5
|
• at P0, the mandible and condylar cartilage are hypoplastic
|
• at P0, the mandibular symphysis is absent
|
• at E14.5 and P0, lower jaw is smaller than normal
|
• at P0, the mandible is still hypoplastic
|
micrognathia
(
J:304767
)
• micrognathia is detected at E14.5 and becomes more severe at P0
|
• at E14.5, palatine bones are absent
|
• Sox9 RNA and protein are upregulated in the frontonasal prominence
|
• mesenchymal cell proliferation is significantly reduced in E12.5 palatal shelves, resulting in lower cell density and smaller palatal shelves with limited ability to grow and fuse by E14.5
|
• at E12.5 and E14.5, Sox9 protein (an early marker of migratory NCCs and a master regulator of chondrogenesis) is ectopically expressed in the palatal shelves
• at E12.5, beta-catenin is downregulated in the palatal mesenchyme along with upregulated Sox9 expression and enhanced Sox9 binding to beta-catenin; Lef1 and Ccnd1 (downstream targets of beta-catenin) are also downregulated in the palatal shelves
• mesenchymal cell proliferation is significantly reduced in E12.5 palatal shelves, resulting in lower cell density and smaller palatal shelves with limited ability to grow and fuse by E14.5
• however, no changes in apoptosis are detected at E12.5 or E14.5
|
• at E14.5 and E17.5, the anterior palatal shelves are hypoplastic and unfused
• 72 hr after ex vivo roller culture, the palatal shelves develop rugae but remain separated and unfused, indicating that cleft palate is independent of tongue development or position
|
• at E14.5 and E17.5, the anterior palatal shelves are hypoplastic
• at E14.5, the volume of palatal shelves is significantly reduced
|
• Sox9 RNA and protein are upregulated in the NCCs colonizing the first pharyngeal arch between E9.5 and E11.5
|
cleft palate
(
J:304767
)
• at E14.5, palatal shelves remain separated by the tongue
|
• by E17.5, the anterior palatal shelves have elevated above the tongue but still remain far apart
• in posterior sections, the palatal shelves grow vertically beside the tongue, fail to elevate and remain separated by the tongue
|
• at E17.5, the tongue is misshapen
|
glossoptosis
(
J:304767
)
• glossoptosis is detected at E14.5 and becomes more severe at P0
|
• at P0, nasal cartilage is hypoplastic or absent
|
skeleton
• at P0, mice exhibit defects in bone development in the skull
|
• at E12.5, Meckels cartilage development is delayed
• at E14.5, Meckels cartilage appears to be loosely organized/packed
• at E12.5 and E14.5, Sox9 is upregulated in Meckels cartilage as well as in the mesenchyme surrounding Meckels cartilage
|
• by E14.5, Meckels cartilage is severely hypoplastic
|
• at P0, mice exhibit defects in cartilage development in the skull
|
• at P0, the frontal bone is underdeveloped
|
• at P0, the temporal bone is underdeveloped; otic bones are hypoplastic
|
• lower incisors are markedly smaller at E17.5
|
• at E17.5, upper incisors are developmentally delayed, having only reached the bell stage, whereas control upper incisors are transitioning from the late bell to eruption stage
• at P0, incisors are underdeveloped
|
• upper and lower molars are developmentally delayed at the bud stage at E14.5 and early bell stage at E17.5
|
• at P0, the mandible and condylar cartilage are hypoplastic
|
• at P0, the mandibular symphysis is absent
|
• at E14.5 and P0, lower jaw is smaller than normal
|
• at P0, the mandible is still hypoplastic
|
micrognathia
(
J:304767
)
• micrognathia is detected at E14.5 and becomes more severe at P0
|
• at E14.5, palatine bones are absent
|
• at P0, nasal cartilage is hypoplastic or absent
|
hearing/vestibular/ear
digestive/alimentary system
• mesenchymal cell proliferation is significantly reduced in E12.5 palatal shelves, resulting in lower cell density and smaller palatal shelves with limited ability to grow and fuse by E14.5
|
• at E12.5 and E14.5, Sox9 protein (an early marker of migratory NCCs and a master regulator of chondrogenesis) is ectopically expressed in the palatal shelves
• at E12.5, beta-catenin is downregulated in the palatal mesenchyme along with upregulated Sox9 expression and enhanced Sox9 binding to beta-catenin; Lef1 and Ccnd1 (downstream targets of beta-catenin) are also downregulated in the palatal shelves
• mesenchymal cell proliferation is significantly reduced in E12.5 palatal shelves, resulting in lower cell density and smaller palatal shelves with limited ability to grow and fuse by E14.5
• however, no changes in apoptosis are detected at E12.5 or E14.5
|
• at E14.5 and E17.5, the anterior palatal shelves are hypoplastic and unfused
• 72 hr after ex vivo roller culture, the palatal shelves develop rugae but remain separated and unfused, indicating that cleft palate is independent of tongue development or position
|
• at E14.5 and E17.5, the anterior palatal shelves are hypoplastic
• at E14.5, the volume of palatal shelves is significantly reduced
|
cleft palate
(
J:304767
)
• at E14.5, palatal shelves remain separated by the tongue
|
• by E17.5, the anterior palatal shelves have elevated above the tongue but still remain far apart
• in posterior sections, the palatal shelves grow vertically beside the tongue, fail to elevate and remain separated by the tongue
|
• at E17.5, the tongue is misshapen
|
glossoptosis
(
J:304767
)
• glossoptosis is detected at E14.5 and becomes more severe at P0
|
growth/size/body
• lower incisors are markedly smaller at E17.5
|
• at E17.5, upper incisors are developmentally delayed, having only reached the bell stage, whereas control upper incisors are transitioning from the late bell to eruption stage
• at P0, incisors are underdeveloped
|
• upper and lower molars are developmentally delayed at the bud stage at E14.5 and early bell stage at E17.5
|
• mesenchymal cell proliferation is significantly reduced in E12.5 palatal shelves, resulting in lower cell density and smaller palatal shelves with limited ability to grow and fuse by E14.5
|
• at E12.5 and E14.5, Sox9 protein (an early marker of migratory NCCs and a master regulator of chondrogenesis) is ectopically expressed in the palatal shelves
• at E12.5, beta-catenin is downregulated in the palatal mesenchyme along with upregulated Sox9 expression and enhanced Sox9 binding to beta-catenin; Lef1 and Ccnd1 (downstream targets of beta-catenin) are also downregulated in the palatal shelves
• mesenchymal cell proliferation is significantly reduced in E12.5 palatal shelves, resulting in lower cell density and smaller palatal shelves with limited ability to grow and fuse by E14.5
• however, no changes in apoptosis are detected at E12.5 or E14.5
|
• at E14.5 and E17.5, the anterior palatal shelves are hypoplastic and unfused
• 72 hr after ex vivo roller culture, the palatal shelves develop rugae but remain separated and unfused, indicating that cleft palate is independent of tongue development or position
|
• at E14.5 and E17.5, the anterior palatal shelves are hypoplastic
• at E14.5, the volume of palatal shelves is significantly reduced
|
cleft palate
(
J:304767
)
• at E14.5, palatal shelves remain separated by the tongue
|
• by E17.5, the anterior palatal shelves have elevated above the tongue but still remain far apart
• in posterior sections, the palatal shelves grow vertically beside the tongue, fail to elevate and remain separated by the tongue
|
• at E17.5, the tongue is misshapen
|
glossoptosis
(
J:304767
)
• glossoptosis is detected at E14.5 and becomes more severe at P0
|
• at P0, nasal cartilage is hypoplastic or absent
|
embryo
N |
• neural crest cell migration is normal at E10.5
|
• Sox9 RNA and protein are upregulated in the NCCs colonizing the first pharyngeal arch between E9.5 and E11.5
|
nervous system
N |
• neural crest cell (NCC) differentiation into neurons of the peripheral nervous system is normal at E10.5
|
cellular
N |
• neural crest cell (NCC) migration and early neuronal differentiation is normal at E10.5
|