FGF signaling in mandibular skeletogenesis

Objective: To examine the functions of FGF/FGFR signaling during mandibular skeletogenesis in ovo. Design: We examined the effects of inhibition of FGF signaling during mandibular skeletogenesis by overexpressing replication-competent RCAS virus encoding a truncated form of FGFR3 in the chicken mandibular process between stages 17 and 26. Results: Injection of RCAS-dnFGFR3 into the developing mandible resulted in abnormalities in a stage-and region-dependent manner. Injection at early stages of development resulted in the truncation of Meckel's cartilage, severely reduced outgrowth of the mandibular process and absence of five of the mandibular bones. Injection at later stages did not affect the outgrowth of the mandibular process and Meckel's cartilage but resulted in abnormalities in mandibular osteogenesis in a region-specific manner. The bones in the more caudal region were frequently truncated whereas bones in the more rostral regions such as dentary and splenial bones were frequently absent. Conclusion: Together these experiments have revealed essential roles for FGF/ FGFR signaling in the elongation of Meckel's cartilage, development of osteogenic condensations and appositional growth of mandibular bones.