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Published on: April 21, 2023
Cdc42 regulates cranial suture morphogenesis and ossification
Ryo Aizawa1, Atsushi Yamada2, Tatsuaki Seki3
1Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan; Department of Periodontology, School of Dentistry, Showa University, Ohta, Tokyo, Japan.
Abstract:
Cdc42 (cell division cycle 42) is ubiquitously expressed small GTPases belonging to the Rho family of proteins. Previously, we generated limb bud mesenchyme-specific Cdc42 inactivated mice (Cdc42 conditional knockout mice; Cdc42 fl/fl; Prx1-Cre), which showed short limbs and cranial bone deformities, though the mechanism related to the cranium phenotype was unclear. In the present study, we investigated the role of Cdc42 in cranial bone development. Our results showed that loss of Cdc42 caused a defect of intramembranous ossification in cranial bone tissues which is related to decreased expressions of cranial suture morphogenesis genes, including Indian hedgehog (Ihh) and bone morphogenetic proteins (BMPs). These findings demonstrate that Cdc42 plays a crucial role in cranial osteogenesis, and is controlled by Ihh- and BMP-mediated signaling during cranium development.
Insights
Cell division cycle 42 (Cdc42) is vital for cranial bone development. Loss of Cdc42 impairs intramembranous ossification by affecting Indian hedgehog and bone morphogenetic protein signaling pathways.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Cdc42 (cell division cycle 42) is a small GTPase in the Rho protein family.
- Previous studies generated Cdc42 conditional knockout mice (Cdc42fl/fl; Prx1-Cre) exhibiting limb and cranial bone deformities, but the cranial mechanism was unknown.
Purpose of the Study:
- To investigate the role of Cdc42 in cranial bone development.
- To elucidate the molecular mechanisms underlying Cdc42's function in osteogenesis.
Main Methods:
- Utilized Cdc42 conditional knockout mice (Cdc42fl/fl; Prx1-Cre) to study cranial bone development.
- Analyzed gene expression related to cranial suture morphogenesis.
Main Results:
- Loss of Cdc42 resulted in defective intramembranous ossification in cranial bone.
- Observed decreased expression of key cranial suture morphogenesis genes, including Indian hedgehog (Ihh) and bone morphogenetic proteins (BMPs).
Conclusions:
- Cdc42 plays a critical role in cranial osteogenesis.
- Cdc42-mediated cranial development is regulated by Ihh- and BMP-signaling pathways.
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