Genetic and hormonal regulation of the death of peptidergic neurons in theDrosophila 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 neuron al apoptosis, we investigated the death of a set of peptidergic neurons in the CNS of the fruitfly Drosophila melanogaster. Typically, apoptosis in Dr osophila is induced by the expression of the genes reaper, grim, or head in volution defective (hid), We provide genetic evidence that the death of the se neurons requires leaper and grim gene function. Consistent with this gen etic analysis, we demonstrate that these doomed neurons accumulate reaper a nd grim transcripts prior to the onset of apoptosis, These neurons also acc umulate 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. W e show that the death of these neurons is dependent upon the fall in the ti ter of the steroid hormone 20-hydroxyecdysone that occurs at the end of met amorphosis, and demonstrate that the accumulation of both reaper and grim t ranscripts is inhibited by this steroid hormone. These observations support the notion that 20E controls apoptosis by regulating the expression of gen es that induce apoptosis, (C) 1999 John Wiley & Sons, Inc.