Recently, in collaboration with Dr. Tickle in England we have demonstrated in chick embryos, that applying a certain group of substances known as FGFs (for fibroblast growth factors) can induce limbs to form where they normally would not. This leads to the supposition that the FGFs are capable of transmitting the limb-growth signal. However none of the applied growth factors is expressed in the correct place or at the correct time in the embryo to be the true limb initiation signal. In this project we propose to study the role of another member of this family of genes, FGF-8. FGF-8 is expressed at the correct time and in the correct place in the developing embryo to initiate the process that leads to the formation of a limb. We will investigate whether applying this gene to the embryo elicits the formation of a limb and we will also try to block the function of these gene during normal development to convince us that FGF-8 is really doing the job of initiating formation of a limb in vivo. Identifying the FGF family member that acts endogenously in limb induction would significantly increase our understanding of vertebrate embryology in general and of limb development in particular. This work should illuminate general mechanisms of cell signaling, which is probably the most important single mechanism that directs appropriate arrangement of tissues and cells in vertebrate embryos.
