Cdc42 regulates cranial suture morphogenesis and ossification.

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. • Cdc42 fl/fl ; Prx1-Cre mice showed Cre recombination in cranial bone tissues. • Loss of Cdc42 caused defect of intramembranous ossification in cranial bone tissues. • The expressions of Ihh , Bmp2 and Bmp4 were down-regulated in cranial bone tissues of Cdc42 fl/fl ; Prx1-Cre mice. [ABSTRACT FROM AUTHOR]