An essential role for the caspase dronc in developmentally programmed celldeath in Drosophila

Drone is a caspase recruitment domain-containing Drosophila caspase that is expressed in a temporally and spatially restricted fashion during developm ent. Drone is the only fly caspase known to be regulated by the hormone ecd ysone. 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, h id, and grim) and enhanced by mutations in diap1. In contrast to previous r eports, 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, Da rk. Furthermore, extracts made from Dark homozygous mutant flies have reduc ed ability to process Drone, showing that Dark is required for Drone proces sing. Finally, using the RNA interference technique, we show that loss of D rone function in early Drosophila embryos results in a dramatic decrease in cell death, indicating that Drone is important for programmed cell death d uring embryogenesis. These results suggest that Drone is a key caspase medi ating programmed cell death in Drosophila.