Localization of TGF-Bs and perlecan in mouse skull development

Post-natal growth of the skull vault occurs by the addition of new bone at the margins of individual calvarial bones. Continued growth depends on the maintenance of a proliferating osteogenic precursor cell population in the sutural membrane between the bones. Mutations in fibroblast growth factor receptors (FGFRs) have recently been detected as the cause of a number of human abnormalities characterized by premature sutural closure, i.e., craniosynostosis. These are activating mutations causing early differentiation of osteogenic precursor cells. Transforming growth factor-betas (TGF-Bs) are another family of developmentally important growth factors. In particular, they play important roles in bone differentiation and are known to be expressed in cranial sutures, and to be upregulated at the time of sutural fusion. It is therefore clear that the FGF and TGF-B signalling pathways interact co-operatively in calvarial bone growth and sutural fusion. The purpose of this study is to investigate this interaction. The long term aim of this work is to gain information that can be used to slow down the process of craniosynostosis after detection of this problem at birth.