Wg and Wnt4 provide long-range directional input to planar cell polarity orientation in Drosophila

Planar cell polarity (PCP) is cellular polarity within the plane of an epithelial tissue or organ. PCP is established through interactions of the core Frizzled(Fz)/PCP factors and although their molecular interactions are beginning to be understood, the upstream input providing directional bias/polarity axis remains unknown. Among core PCP genes, Fz is unique as it regulates PCP both cell-autonomously and non-autonomously, with the extra-cellular domain of Fz acting as a ligand for Van-Gogh (Vang). We demonstrate in Drosophila wings that Wg and dWnt4 provide instructive regulatory input for PCP axis determination, establishing polarity axes along their graded distribution and perpendicular to their expression domain borders. Loss-of-function studies reveal that Wg/dWnt4 act redundantly in PCP determination. They affect PCP by modulating the intercellular interaction between Fz and Vang, which is thought to be a key step in setting up initial polarity, thus providing directionality to the PCP process.