Multiple functions of fibroblast growth factors in vertebrate development.

The biological consequences of ectopic FGF-4 expression were examined in chimaeric mouse embryos prepared with ES cells constitutively expressing FGF-4. The embryos exhibit abnormalities of the limbs and the anterior central nervous system. The limb phenotype consisted of the induction of early phases of limb development along the lateral ridge between the definitive fore and hind limb buds, where normally no limb outgrowth takes place. This phenotype was examined further by the implantation of beads soaked in FGF into the flank of developing chick embryos. This resulted in the induction of complete supernumerary limbs containing skeletal structures. These results indicated that FGFs have the ability to induce the outgrowth of limbs in an ectopic site and implicate FGFs in the initiation of normal limb development.