HISTORICAL BACKGROUND

The discovery of fibroblast growth factors (FGFs) in the 1970s arose from observations that a protein with a basic isoelectric point of 9.6, derived from bovine brain and pituitary gland, was able to induce morphological changes in BALB/c 3T3 fibroblast cells (1). Early limitations in purifying the growth factor led to the belief that the FGF derived from bovine brains was a component of myelin basic protein (2). This claim was countered by several reports of nonassociation between the two proteins (3,4), yet the definitive purification did not occur until 1984, when heparin Sepharose chromatography was used to effectively isolate FGFs (5). An acidic fibroblast growth factor (isoelectric point 5.6) was identified several years after the discovery of basic fibroblast growth factor (6–8).

In 1991, when seven FGFs had been identified, a nomenclature committee renamed aFGF and bFGF as FGF1 and FGF2, respectively (9).

EVOLUTION

In Caenorhabditis elegans, two FGF genes (egg laying defective 17 [egl-17] and lethal-75 [let-75]), and one FGF receptor (FGFR) gene (egl-15) are identified. The fruit fly, Drosophila melanogaster, has three FGF genes, branchless, pyramus, and thisbe and two FGFR genes, breathless and heartless. Early in evolution, Fgfs have undergone a gene duplication expanding from two or three to six genes; thereafter, a second gene duplication occurred during evolution of the early vertebrates, resulting in 22 FGF genes in mice and humans (FGF1–23) (human FGF15 and mouse Fgf19 have not been identified in the genome, and mouse Fgf15 and human FGF19 are now thought to be orthologous genes [10]).