COOPERATIVE FUNCTIONS OF THE REAPER AND HEAD INVOLUTION DEFECTIVE GENES IN THE PROGRAMMED CELL-DEATH OF DROSOPHILA CENTRAL-NERVOUS-SYSTEM MIDLINE CELLS

In Drosophila, the chromosomal region 75C1-2 contains at least three g enes, reaper (rpr), head involution defective (hid), and grim, that ha ve important functions in the activation of programmed cell death. To better understand how cells are killed by these genes, we have utilize d a well defined set of embryonic central nervous system midline cells that normally exhibit a specific pattern of glial cell death. In this study we show that both rpr and hid are expressed in dying midline ce lls and that the normal pattern of midline cell death requires the fun ction of multiple genes in the 75C1-2 interval. We also utilized the P [UAS]/P[Gal4] system to target expression of rpr and hid to midline ce lls. Targeted expression of rpr or hid alone was not sufficient to ind uce ectopic midline cell death. However, expression of both rpr and hi d together rapidly induced ectopic midline cell death that resulted in axon scaffold defects characteristic of mutants with abnormal midline cell development. Midline-targeted expression of the baculovirus p35 protein, a caspase inhibitor, blocked both normal and ectopic rpr- and hid-induced cell death. Taken together, our results suggest that rpr and hid are expressed together and cooperate to induce programmed cell death during development of the central nervous system midline.