ROLES FOR FGF8 IN THE INDUCTION, INITIATION, AND MAINTENANCE OF CHICKLIMB DEVELOPMENT

We provide evidence that FGF8 serves as an endogenous inducer of chick limb formation and that its expression in the intermediate mesoderm a t the appropriate time and place to trigger forelimb development is di rectly linked to the mechanism of embryonic kidney differentiation. On e function of the limb inducer is to initiate Fgf8 gene expression in the ectoderm overlying the prospective limb-forming territories. FGF8 secreted by the ectoderm then appears to initiate limb bud formation b y promoting outgrowth of and Sonic hedgehog expression in the underlyi ng lateral plate mesoderm. FGF8 also maintains mesoderm outgrowth and Sonic hedgehog expression in the established limb bud. Our data thus p oint to FGF8 as a key regulator of limb development that not only indu ces and initiates the formation of a limb bud, but also sustains its s ubsequent development.