Fgf-8 is a member of the fibroblast growth factor (FGF) family that was initially identified as an androgen-inducible growth factor in a mammary carcinoma cell line. Fgf-8 is one of the key signaling molecules implicated in the initiation, outgrowth, and patterning of vertebrate limbs. The cloned 1.26-kb cDNA contained an open reading frame encoding 212 amino acid residues with 84%, 86%, and 80% amino acid identities to those of Xenopus, chick, and mouse, respectively. None of the FGF-8 isoforms exhibited activity to FGFR1b, 2b, 3b, but FGFR2c, 3c and FGFR4 can be activated by several FGF-8 isoforms. FGF-8 plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration, and it is required for normal brain, eye, ear and limb development during embryogenesis. FGF-8 shows limited expression in the normal adult, but low levels are found in the reproductive and genitourinary tract, peripheral leukocytes and bone marrow hematopoietic cells.