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FGF signaling in mandibular skeletogenesis
Mina Mina1, Bruce Havens, D A Velonis
1Division of Pediatric Dentistry, Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA. mina@nso1.uchc.edu
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.
Insights
Fibroblast Growth Factor (FGF) signaling is crucial for mandibular bone development. Inhibiting FGF receptor 3 (FGFR3) in ovo disrupts Meckel
Area of Science:
- Developmental biology
- Skeletal biology
- Molecular signaling
Background:
- Fibroblast Growth Factor (FGF) and FGF Receptor (FGFR) signaling pathways regulate diverse developmental processes.
- Mandibular skeletogenesis, the formation of the lower jaw, involves complex cellular and molecular interactions.
Purpose of the Study:
- To investigate the role of FGF/FGFR signaling in avian mandibular bone development (skeletogenesis) in ovo.
- To elucidate the specific functions of FGF/FGFR signaling during the formation of the lower jaw.
Main Methods:
- Utilized a replication-competent avian retrovirus (RCAS) to overexpress a dominant-negative form of FGFR3 (dnFGFR3).
- Inhibited FGF signaling within the developing chicken mandible between embryonic stages 17 and 26.
- Analyzed the effects on Meckel's cartilage, mandibular process outgrowth, and bone formation.
Main Results:
- Inhibition of FGF signaling led to stage- and region-dependent abnormalities in mandibular development.
- Early inhibition caused Meckel's cartilage truncation, reduced mandibular outgrowth, and absence of several bones.
- Later inhibition affected mandibular osteogenesis, with caudal bones truncated and rostral bones (dentary, splenial) often absent.
Conclusions:
- FGF/FGFR signaling is essential for Meckel's cartilage elongation during mandibular development.
- This signaling pathway plays a critical role in the development of osteogenic condensations.
- FGF/FGFR signaling is vital for the appositional growth of mandibular bones.
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