Roles of FGFR3 during morphogenesis of Meckel's cartilage and mandibular bones.
To address the functions of FGFR2 and FGFR3 signaling during mandibular skeletogenesis, we over-expressed in the developing chick mandible, replication-competent retroviruses carrying truncated FGFR2c or FGFR3c that function as dominant negative receptors (RCAS-dnFGFR2 and RCAS-dnFGFR3). Injection of RCAS-dnFGFR3 between HH15 and 20 led to reduced proliferation, increased apoptosis, and decreased differentiation of chondroblasts in Meckel's cartilage. These changes resulted in the formation of a hypoplastic mandibular process and truncated Meckel's cartilage. This treatment also affected the proliferation and survival of osteoprogenitor cells in osteogenic condensations, leading to the absence of five mandibular bones on the injected side. Injection of RCAS-dnFGFR2 between HH15 and 20 or RCAS-dnFGFR3 at HH26 did not affect the morphogenesis of Meckel's cartilage but resulted in truncations of the mandibular bones. RCAS-dnFGFR3 affected the proliferation and survival of the cells within the periosteum and osteoblasts. Together these results demonstrate that FGFR3 signaling is required for the elongation of Meckel's cartilage and FGFR2 and FGFR3 have roles during intramembranous ossification of mandibular bones.
Havens
Bruce A
BA
Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Velonis
Dimitris
D
Kronenberg
Mark S
MS
Lichtler
Alex C
AC
Oliver
Bonnie
B
Mina
Mina
M
D000818:Animals; D002356:Cartilage / Q000196:embryology*; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D005260:Female; D008334:Mandible / Q000196:embryology*; D009024:Morphogenesis / Q000502:physiology*; D010012:Osteogenesis; D010063:Ovum / Q000502:physiology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000502:physiology; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D015398:Signal Transduction
D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3