FIBROBLAST GROWTH-FACTORS INDUCE ADDITIONAL LIMB DEVELOPMENT FROM THEFLANK OF CHICK-EMBRYOS

Fibroblast growth factors (FGFs) act as signals in the developing limb and can maintain proliferation of limb bud mesenchyme cells. Remarkab ly, beads soaked in FGF-1, FGF-2, or FGF-4 and placed in the presumpti ve flank of chick embryos induce formation of ectopic limb buds, which can develop into complete limbs. The entire flank can produce additio nal limbs, but generally wings are formed anteriorly and legs posterio rly. FGF application activates Sonic hedgehog in cells with polarizing potential to make a discrete polarizing region. Hoxd-13 is also expre ssed in the ectopic bud, and an apical ectodermal ridge forms. A limb bud is thus established that can generate the appropriate signals to d evelop into a complete limb. The additional limbs have reversed polari ty. This can be explained by the distribution of cells in the flank wi th potential polarizing activity. The results suggest that local produ ction of an FGF may initiate limb development.