FGF Receptor Expression in the Perisutural Tissues of Craniosynostotic Rabbits

Objective: Recent studies have demonstrated that mutations in various fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3) result in a myriad of dysostotic syndromes (i.e, Crouzon, Apert, Muenke). The purpose of the present study is to describe the expression patterns of these growth factor receptors (FGFR1, FGFR2, FGFR3) in the perisutural tissues of a rabbit model of craniosynostosis to help elucidate the etiopathogenesis of this condition. Methods: Twenty coronal sutures were harvested from 10, 10 day old New Zealand white rabbits: five wild type, control rabbits (n = 10 coronal sutures), and five rabbits with familial coronal suture synostosis (n = 10 coronal sutures). All rabbits were obtained from the synostosed breeding colony at the University of Pittsburgh. At ten days of age the rabbits were euthanized, the calvariae were harvested en bloc and processed for immunohistochemistry. The periosteum, dura mater, osteogenic fronts of the coronal suture, and sutural ligament were stained for the presence of FGFR1, FGFR2, and FGFR3 using an indirect immunoperoxidase procedure with isoform specific antibodies. Staining intensity by tissue type and group were ranked by three investigators for each receptor and statistically evaluated using a chi-square analysis. Results: A significant (p<0.05) and highly differential staining pattern was observed for FGFR-1 in the periosteum and osteogenic fronts in which FGFR-1 was more abundant in wild-type rabbits compared to the synostosed rabbits. No significant differences (p>0.05) in staining intensity were observed between tissue types or groups for either FGFR-2 or FGFR-3. Conclusion: These findings suggest that FGF receptor expression at 10 days of age probably does not play a maintenance role in synostosis in this rabbit model. However, further receptor-localization and receptor-function data is needed from fetal rabbit sutures to validate this conclusion.