Fibroblast growth factors in the nervous system

Fibroblast growth factors (FGFs) exhibit widespread mitogenic and neurotrophic activities. Nine members of the family are currently known, and FGF-1 and FGF-2 are present in relatively high levels in CNS. FGF-1 is expressed by a subset of neuronal populations, while FGF-2 is expressed by astrocytes. FGF-1 and FGF-2 lack signal peptides and appear to be present mainly in intracellular compartments. This suggests that the factors may act as initiators of a repair response after injury. Support for this notion comes from observations that FGF-1 and FGF-2 levels are low during critical phases of development, but high in the adult CNS. A family of transmembrane tyrosine kinase receptors (FGFRs) mediates the effects of FGFs. Four different genes coding for FGF receptors are currently known, three of which are expressed in cell type-specific patterns in the CNS. The main receptor variants present in this tissue, however, can by themselves not distinguish between FGF-1 and FGF-2. Additional selectivity may be established by interaction of the FGFs and their receptors with select heparan proteoglycans (HSPGs). Therefore, the precise physiological role of FGFs is determined by the combination of cell type-specific patterns of expression of FGFs, FGFRs and HSPGs together with the mechanisms that regulate the extracellular availability of FGFs.