View Program - 63rd Annual Drosophila Research Conference

There is increasing recognition that cells may activate apoptotic caspases but not die, instead displaying various physiologically relevant consequences. We know very little, however, of mechanisms that underlie the life/death decision in a cell that has activated apoptotic caspases. By optimizing a published reporter of past caspase activity, we have been able to visualize such cells that result specifically from exposure to ionizing radiation (IR) in Drosophila larval wing discs. We found that cells with X-ray-induced past active caspases (XPAC) do not arise at random but are born at specific locations within the developing wing imaginal discs of Drosophila larvae. Furthermore, this reporter has allowed us to gather pre-liminary data on genes that might influence the number of XPAC. Axin, a negative regulator of wingless signaling, increases the number of XPAC cells suggesting that wingless signaling regulates whether cells with caspase activity live or die. A dosage response curve shows that the number of XPAC reaches a peak and then decreases at higher radiation doses. We also found that heterozygotes of H99 chromosomal deficiency that removes pro-apoptotic genes hid, rpr and grim show reduced number of XPAC cells. Yet, XPAC cells appear in stereotypical patterns that do not follow the pattern of IR-induced apoptosis, suggesting additional controls at play. By following irradiated larvae into adulthood, we found that XPAC cells contribute to the adult wing. By combining a reporter for past caspase activity with mwh, an adult marker for Loss of Heterozygosity (LOH), we addressed the relationship between XPAC and genome stability after irradiation. We find that XPAC cells show reduced LOH relative to the rest of the wing, suggesting a physiological role for non-lethal caspase activity during recovery from radiation damage.

Ionizing Radiation induces cells with past caspase activity that contribute to the adult organ in Drosophila and show reduced Loss of Heterozygosity

**Ionizing Radiation induces cells with past caspase activity that contribute to the adult organ in Drosophila and show reduced Loss of Heterozygosity**