Factor’s role in long bone developmentJul. 31, 2013, 8:00 AM
The fibroblast growth factors and their receptors (FGFR) play important roles in skeletal development, and genetic mutations that activate FGFR cause syndromes that include short stature, or dwarfism.
Florent Elefteriou, Ph.D., and colleagues in the Vanderbilt Center for Bone Biology, have explored the signaling pathway of FGFR using genetic mouse models. They report in the Aug. 1 issue of Human Molecular Genetics that the protein neurofibromin restrains FGFR signaling in chondrocytes – the cells that contribute to the formation of the skeleton’s long bones. Mice missing neurofibromin show evidence of dwarfism (like mice with activating mutations in FGFR). The investigators demonstrate that neurofibromin, acting as a negative regulator of the protein Ras, is required for proper chondrocyte proliferation and maturation and other critical growth plate processes.
The studies suggest that the severe delay in fracture healing in some patients with neurofibromatosis type I (an inherited tumor disorder caused by mutations in the gene for neurofibromin 1) may benefit from treatments that block overactive components of FGFR signaling.
This research was supported by a grant from the Department of Defense.