The appendages of insects, like the limbs of vertebrates, grow out of the body wall after the establishment of a proximo-distal axis among a group of primordial cells. In Drosophila, the wing develops in the limbless larva from one of the imaginal discs of the thorax, which give rise to the adult epidermis. The earliest identified requirement in wing development is for the induction of vestigial (vg) gene expression at the interface between ventral cells and dorsal cells of the wing disc. It has been proposed that this event requires two reciprocal signals--one from the dorsal to the ventral cells and the other from the ventral to the dorsal cells--which trigger vg expression at the presumptive wing margin and hence initiate the development of the wing tissue.We have identified four genes--Serrate (Ser), wingless (wg), Notch and Suppressor of Hairless (Su(H))--whose activity is required during the second and early third larval instars for the expression of vg. Analysis of the functions and patterns of expression of these genes at the time of the inductive event indicates that the Ser protein acts as a dorsal signal, and the Wg protein as a ventral signal for the induction of vg expression. Furthermore, the expression of both Ser and Wg is sufficient to trigger ectopic wing development in the wing disc and leg discs. The product of the Notch gene, which encodes a receptor, is also required for this event and we suggest that its role is to integrate the inputs of Ser and Wg.We show that the induction of vg, which initiates wing development in Drosophila, requires the combined activities of Ser, wg and Notch. Based on the patterns of expression and requirements for Ser and wg in this process, we propose that Ser is a dorsal signal and that Wg is a ventral signal, and that their combination at the dorso-ventral interface activates the Notch receptor and leads to vg expression.