New insights in the mechanisms of craniosysnostosis

We demonstrated that Noggin is expressed in sutures that are destined to remain patent. In marked contrast, fusing suture expresses no Noggin. Although researchers have postulated that suture patency is a passive process resulting from insufficient levels of osteogenic cytokines, we have demonstrated that Noggin actively maintains suture patency by inactivating BMPs. Recently, investigators have linked FGFR gain-of-function mutations with syndromic craniosynostoses. First, we demonstrated that FGF-2 protein and FGF-2 overexpression adenovirus suppreseds Noggin production in vitro and in vivo. Next, we demonstrated that human Apert and Crouzon FGFR2 mutations suppressed Noggin. Finally, we found that Noggin misexpression prevented sutures fusion. Collectively, these data provide mechanistic explanation for premature suture fusion in some forms of syndromic craniosynostosis.