OVERLAPPING EXPRESSION AND REDUNDANT ACTIVATION OF MESENCHYMAL FIBROBLAST GROWTH-FACTOR (FGF) RECEPTORS BY ALTERNATIVELY SPLICED FGF-8 LIGANDS

FGF-8 is a member of the family of fibroblast growth factors and is ex pressed during vertebrate embryo development, Eight potential FGF-8 is oforms are generated by alternative splicing in mice, several of which are expressed during embryogenesis in epithelial locations, The signi ficance of the multiple isoforms is currently unknown, In this report, we investigate the expression patterns and the specificity of the FGF -8 isoforms for known fibroblast growth factor (FGF) receptors, RNAs f or seven of the eight potential isoforms are present at multiple sites of embryonic Fgf8 expression, None of the FGF-8 isoforms exhibited ac tivity when assayed with BaF3 cells expressing the ''b'' splice forms of FGF receptors 1-3, which are mostly expressed in epithelial tissues , Mesenchymally expressed ''c'' splice forms of FGF receptors 2 and 3 and FGF receptor 4 were activated by several FGF-8 isoforms. These fin dings are consistent with the hypothesis that the multiple FGF-8 isofo rms are functionally redundant and function to signal in paracrine (ep ithelial to mesenchymal) contexts.