An essential role for the caspase dronc in developmentally programmed cell death in Drosophila

Drone is a caspase recruitment domain-containing Drosophila caspase that is expressed in a temporally and spatially restricted fashion during development. Drone is the only fly caspase known to be regulated by the hormone ecdysone. Here we show that ectopic expression of drone in the developing fly eye leads to increased cell death and an ablated eye phenotype that can be suppressed by halving the dosage of the genes in the H99 complex (reaper, hid, and grim) and enhanced by mutations in diap1. In contrast to previous reports, we show that the drone eye ablation phenotype can be suppressed by coexpression of the baculoviral caspase inhibitor p35. Drone also interacts, both genetically and biochemically, with the CED-4/Apaf-1 fly homolog, Dark. Furthermore, extracts made from Dark homozygous mutant flies have reduced ability to process Drone, showing that Dark is required for Drone processing. Finally, using the RNA interference technique, we show that loss of Drone function in early Drosophila embryos results in a dramatic decrease in cell death, indicating that Drone is important for programmed cell death during embryogenesis. These results suggest that Drone is a key caspase mediating programmed cell death in Drosophila.