Novel Roles for FGFR Signaling During Mandibular Outgrowth and Chondrogenesis

Fgf/Fgfr signaling is an important signaling pathway involved in mandibular morphogenesis. However, the ligands and receptors regulating this process are largely unknown. All four Fgf receptors are expressed during mandibular morphogenesis in a temporally and spatially regulated way. Previous results from our laboratory showed over-expression of a dominant-negative FGFR3 (dnFgfr3) in the developing mandible resulted in a wide range of abnormalities, including truncation of the mandibular process and Meckel's cartilage (MC) on the treated side. Objectives: To understand the underlying mechanisms by which dnFGFR3 leads to reduced outgrowth of the mandibular processes. Methods: RCAS-dnFgfr3c vector was injected in ovo into the right half of developing chick mandibles between stages 17-20. At various time intervals, embryos were isolated and processed for in situ hybridization, wholemount skeletal staining, quantitative morphological analysis, proliferation and apoptosis assays. Results: The unchanged patterns of expression of a variety of early regulatory genes in the treated side indicated that the truncation of the developing mandible was not related to disturbances in signaling cascades regulating mandibular outgrowth and morphogenesis. Over-expression of dnFGFR3 did not affect the initiation of MC formation, but affected the further growth and differentiation of the condensing mesenchyme giving rise to the elongated MC rod. The condensing mesenchyme on the treated side displayed increased apoptosis, a smaller domain and decreased levels of expression of the chondrogenic marker Sox9 followed by decreased proliferation. However, during later stages, the number and distribution of proliferating cells in the truncated MC were quantitatively indistinguishable from the MC on the untreated side. Conclusion: These observations indicate the positive roles of Fgf/Fgfr3 in the survival, proliferation, and differentiation of the mesenchymal condensation that forms MC. Furthermore, our results demonstrate that the outgrowth of the mandible is dependent on the proper development and outgrowth of MC. Supported by DE08682 & DE07302.

*2152 Novel Roles for FGFR Signaling During Mandibular Outgrowth and Chondrogenesis*
B. HAVENS¹, A.E. DOUFEXI², and M. MINA², ¹University of Connecticut Health Center, School of Dental Medicine, Farmington, USA, ²University of Connecticut Health Center, Farmington, USA Fgf/Fgfr signaling is an important signaling pathway involved in mandibular morphogenesis. However, the ligands and receptors regulating this process are largely unknown. All four Fgf receptors are expressed during mandibular morphogenesis in a temporally and spatially regulated way. Previous results from our laboratory showed over-expression of a dominant-negative FGFR3 (dnFgfr3) in the developing mandible resulted in a wide range of abnormalities, including truncation of the mandibular process and Meckel's cartilage (MC) on the treated side. Objectives: To understand the underlying mechanisms by which dnFGFR3 leads to reduced outgrowth of the mandibular processes. Methods: RCAS-dnFgfr3c vector was injected in ovo into the right half of developing chick mandibles between stages 17-20. At various time intervals, embryos were isolated and processed for in situ hybridization, wholemount skeletal staining, quantitative morphological analysis, proliferation and apoptosis assays. Results: The unchanged patterns of expression of a variety of early regulatory genes in the treated side indicated that the truncation of the developing mandible was not related to disturbances in signaling cascades regulating mandibular outgrowth and morphogenesis. Over-expression of dnFGFR3 did not affect the initiation of MC formation, but affected the further growth and differentiation of the condensing mesenchyme giving rise to the elongated MC rod. The condensing mesenchyme on the treated side displayed increased apoptosis, a smaller domain and decreased levels of expression of the chondrogenic marker Sox9 followed by decreased proliferation. However, during later stages, the number and distribution of proliferating cells in the truncated MC were quantitatively indistinguishable from the MC on the untreated side. Conclusion: These observations indicate the positive roles of Fgf/Fgfr3 in the survival, proliferation, and differentiation of the mesenchymal condensation that forms MC. Furthermore, our results demonstrate that the outgrowth of the mandible is dependent on the proper development and outgrowth of MC. Supported by DE08682 & DE07302.
Seq #237 - Fluoride/Cartilage and Chondrogenesis 2:00 PM-4:00 PM, Friday, 11 March 2005 Baltimore Convention Center Exhibit Hall E-F
Back to the Mineralized Tissue Program Back to the IADR/AADR/CADR 83rd General Session (March 9-12, 2005)
Top Level Search