Cdc42 regulates cranial suture morphogenesis and ossification

Abstract Cdc42( cell division cycle42) is ubiquitously expressed small GTPasesbelonging to the Rho family of proteins. Previously, we generated limb budmesenchyme-specific Cdc42inactivated mice ( Cdc42conditional knockout mice; Cdc42 fl/fl ; Prx1-Cre ), which showed short limbs and cranial bonedeformities, though the mechanism related to the cranium phenotype was unclear. In the present study, we investigated the role of Cdc42in cranial bonedevelopment. Our results showed that loss of Cdc42caused a defect of intramembranous ossificationin cranial bonetissues which is related to decreased expressions of cranial suturemorphogenesis genes, including Indian hedgehog(Ihh) and bone morphogenetic proteins(BMPs). These findings demonstrate that Cdc42plays a crucial role in cranial osteogenesis, and is controlled by Ihh- and BMP-mediated signaling during cranium development.