PANGOLIN ENCODES A LEF-1 HOMOLOG THAT ACTS DOWNSTREAM OF ARMADILLO TOTRANSDUCE THE WINGLESS SIGNAL IN DROSOPHILA

Members of the Wnt/Wingless (Wg) family of signalling proteins organiz e many aspects of animal development by regulating the expression of p articular target genes in responding cells(1-6). Recent biochemical st udies(7-9) indicate that the vertebrate HMG-domain proteins Lef-1 and XTcf-3 can physically interact with beta-catenin, a homologue of Droso phila Armadillo (Arm), the most downstream component known in the Wnt signal transduction pathway(10,11). However, these studies do not addr ess whether the endogenous Lef/Tcf family members are required in vivo to transduce Wnt signals. Using genetic methods in Drosophila, we def ine a new segment polarity gene, pangolin (pan), and show that its pro duct is required in vivo for Wg signal transduction in embryos and in developing adult tissues. In addition, we show that pan encodes a Lef/ Tcf homologue and provide evidence that its protein product binds to t he beta-catenin homologue Armadillo in vivo, Finally, we demonstrate t hat Pan functions downstream of Arm to transduce the Wg signal. Thus, our results indicate that Pan is an essential component of the Wg tran sduction pathway and suggest that it acts directly to regulate gene tr anscription in response to Wg signalling.