A collection of split-Gal4 drivers targeting conserved signaling ligands in Drosophila

Communication between cells in metazoan organisms is mediated by a remarkably small number of highly conserved signaling pathways. Given this small number of signaling pathways, the existence of multiple related ligands for many of these pathways represents a key evolutionary innovation for encoding complexity into cell-cell signaling. Relatedly, crosstalk between pathways is another critical feature, which allows a modest number of pathways to ultimately generate an enormously diverse range of outcomes. It would thus be useful to have genetic tools to identify and manipulate not only those cells that express a given signaling ligand but also those cells that specifically coexpress pairs of signaling ligands. We present a collection of split-Gal4 knock-in lines targeting many of the ligands for highly conserved signaling pathways in Drosophila (Notch, Hedgehog, fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor β (TGFβ), Janus kinase/signal transducer and activator of transcription (JAK/STAT), Jun kinase (JNK), and platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF)-related receptor (PVR). We demonstrate that these lines faithfully recapitulate the endogenous expression pattern of their targets and that they can be used to identify cells and tissues that coexpress pairs of ligands. As a proof of principle, we demonstrate that the 4th chromosome TGFβ ligands myoglianin and maverick are broadly coexpressed in muscles and other tissues of both larva and adults and that the JAK/STAT ligands upd2 and upd3 are partially coexpressed from cells of the midgut following gut damage. Together with our previously collection of split-Gal4 lines targeting the 7 Wnt ligands, this resource allows Drosophila researchers to identify and genetically manipulate cells that specifically express pairs of conserved ligands from nearly all the major intercellular signaling pathways.