FGFs, heparan sulfate and FGFRs: complex interactions essential for development

Fibroblast growth factors (FGFs) comprise a large family of developmental a nd physiological signaling molecules. All FGFs have a high affinity for the glycosaminoglycan heparin and for cell surface heparan sulfate proteoglyca ns. A large body of biochemical and cellular evidence points to a direct ro le for heparin/heparan sulfate in the formation of an active FGF/FGF recept or signaling complex. However, until recently there has been no direct demo nstration that heparan is required for the biological activity of FGF in a developmental system in vivo. A recent paper by Lin et al.((1)), has broken through this barrier to demonstrate that heparan sulfate is essential for FGF function during Drosophila development. The establishment of a role for heparan sulfate in FGFR activation in vivo suggests that tissue-specific d ifferences in the structure of heparan may modulate the activity of FGF. (C ) 2000 John Wiley & Sons, Inc.