Simultaneous induction of apoptosis, collagen type I expression and mineralization in the developing coronal suture following FGF4 and FGF2 application

This study aimed to evaluate the disturbances in normal coronal suture deve lopment resulting in craniosynostosis, a congenital disorder in which the c alvarial sutures close prematurely. Craniosynostosis syndromes can be cause d by mutations in the genes encoding for the fibroblast growth factor recep tors (FGFRs) 1, 2, and 3. These gain-of-function mutations cause the transc ribed receptor to be constitutively activated. To mimic this genetic defect , fibroblast growth factor (FGF) 2 or 4 was administered near the developin g coronal suture in normal mouse embryos through ex utero surgery. The effe ct on apoptosis and bone differentiation, as collagen type I expression and mineralization, within the FGF-exposed coronal suture was investigated thr ough (immuno)histochemical staining. An increase in the number of apoptotic cells together with ectopic collagen type I expression within the suture a nd accelerated mineralization followed FGF application. Macroscopically, th is presented as a synostotic coronal suture. These results suggest that bot h apoptosis and differentiation are two processes that are simultaneously i mplicated in synostosis of the coronal suture in case of a FGFR-related cra niosynostosis.