Expression of high-affinity receptors for TGF-beta during rat cranial suture fusion

The etiology of craniosynostosis is unknown. The elucidation of the biologi cal pathways responsible for this disorder has been hampered by an inabilit y to evaluate cranial sutures before, during, and after cranial suture fusi on. The programmed fusion of the rat posterofrontal (PF) suture postnatally provides an excellent model to study the molecular events that occur durin g cranial suture fusion. Previous experiments have implicated transforming growth factor beta (TGF-beta) growth factors in the regulation of PF suture fusion. The purpose of these experiments was to localize the expression of high-affinity receptors for these growth factors during cranial suture fus ion. Four rats were sacrificed on postnatal days 8, 12, 17, and 40 (N = 16) . The PF and sagittal sutures were harvested and prepared for immunohistoch emical localization of TGF-beta receptor 1 and receptor 2 (T beta-RI, T bet a-RII) protein. Results indicate that immunostaining for T beta-RI and T be ta-RII is markedly increased in the dura mater and osteoblasts of the sutur al margin of the PF suture during active suture fusion (on postnatal days 1 2, 17, and 40) compared with the osteoblasts and dura mater underlying the patent sagittal suture. These results, in combination with the authors' pre vious findings as well as studies supporting a role for TGF-beta molecules in the regulation of osteogenesis, implicate TGF-beta signaling in the regu lation of suture fusion. The possible mechanisms of ligand-receptor interac tion are discussed.