In vivo modulation of FGF biological activity alters cranial suture fate

Gain-of-function mutations in fibroblast growth factor receptors have been identified in numerous syndromes associated with premature cranial suture f usion. Murine models in which the posterior frontal suture undergoes progra mmed fusion after birth while all other sutures remain patent provide an id eal model to study the biomolecular mechanisms that govern cranial suture f usion, Using adenoviral vectors and targeted in utero injections in rats, w e demonstrate that physiological posterior frontal suture fusion is inhibit ed using a dominant-negative fibroblast growth factor receptor-1 construct, whereas the normally patent coronal suture fuses when infected with a cons truct that increases basic fibroblast growth factor biological activity. Ou r data may facilitate the development of novel, less invasive treatment opt ions for children with craniosynostosis.