[Frontiers in Bioscience 3, d781 -794, August 1, 1998] |
FGF SIGNALING IN SKELETAL DEVELOPMENT
Michael C. Naski and David M. Ornitz
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Campus Box 8103, 660 S. Euclid Ave., St. Louis, MO 63110
Received12/22/98 Accepted 2/17/98
Many recent developments in the biology of FGF receptor signaling have furthered our understanding of the role of these molecules during skeletogenesis. These include the identification of the various skeletal dysplasias that result from mutations in the FGF receptors, the biochemical characterization of the effect of these mutations on receptor function, and the additional characterization of the pleotropic effects of FGFs during limb development, suture formation and endochondral ossification.
Notwithstanding this progress, many questions remain to be answered. While several receptor mutations are known to be gain of function mutations, the effect of many others on receptor activity are unknown. Some of these mutations may alter ligand binding affinity or receptor dimerization. A greater understanding of the biochemical properties of the mutant receptors will help to decipher the specific ligand-receptor pairs that function during Development The possibility of direct or indirect interactions between different receptors harboring mutations must also be investigated. Animal models for both the craniosynostosis and dwarfing conditions will be essential to fully understand the effects of FGFs during the complicated processes of osteoblast and chondrocyte differentiation. The compilation of these studies will hopefully link receptor biochemistry and skeletogenesis and guide future efforts to modulate FGF receptor activity for clinical benefit.