Genetic and hormonal regulation of the death of peptidergic neurons in the Drosophila central nervous system.

To understand the role apoptosis plays in nervous system development and to gain insight into the mechanisms by which steroid hormones regulate neuronal apoptosis, we investigated the death of a set of peptidergic neurons in the CNS of the fruitfly Drosophila melanogaster. Typically, apoptosis in Drosophila is induced by the expression of the genes reaper, grim, or head involution defective (hid). We provide genetic evidence that the death of these neurons requires reaper and grim gene function. Consistent with this genetic analysis, we demonstrate that these doomed neurons accumulate reaper and grim transcripts prior to the onset of apoptosis. These neurons also accumulate low levels of hid, although the genetic analysis suggests that hid may not play a major role in the induction of apoptosis in these neurons. We show that the death of these neurons is dependent upon the fall in the titer of the steroid hormone 20-hydroxyecdysone that occurs at the end of metamorphosis, and demonstrate that the accumulation of both reaper and grim transcripts is inhibited by this steroid hormone. These observations support the notion that 20E controls apoptosis by regulating the expression of genes that induce apoptosis.