Fibroblast growth factors (FGFs) comprise a family of 22 distinct proteins with pleiotropic signaling functions in development and homeostasis. These functions are mediated principally by four fibroblast growth factor receptors (FGFRs), members of the receptor tyrosine kinase family, with heparin glycosaminoglycan as an important cofactor. Developmental studies in chick and mouse highlight the critical role of FGF-receptor signaling in multiple phases of limb development, including the positioning of the limb buds, the maintenance of limb bud outgrowth, the detailed patterning of the limb elements, and the growth of the long bones. Corroborating these important roles, mutations of two members of the FGFR family (FGFR1 and FGFR2) are associated with human disorders of limb patterning; in addition, mutations of FGFR3 and FGF23 affect growth of the limb bones. Analysis of FGFR2 mutations in particular reveals a complex pattern of genotype/phenotype correlation, which will be reviewed in detail VSports手机版. Circumstantial evidence suggests that the more severe patterning abnormalities are mediated by illegitimate paracrine signaling in the mesoderm, mediated by FGF10 or by a related FGF, and this is beginning to gain some experimental support. A further test of this hypothesis is provided by a unique family segregating two FGFR2 mutations in cis (S252L; A315S), in which severe syndactyly occurs in the absence of the craniosynostosis that typically accompanies FGFR2 mutations. .