211C Poster - 01. Cell Stress and cell death
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Jessica Sawyer; Ruth Montague; Dongwon Lee; Don Fox

Affiliation: Duke University

Keywords:
a. caspases; k. regeneration

Quiescent long-lived cells often resist many types of cellular insults, which is an advantage in tissues with limited regenerative capacity. However, the molecular underpinnings that promote cellular longevity within a tissue are still largely unclear. We have established the adult hindgut of Drosophila melanogaster as a model to understand responses to cell death in a long-lived, low cell turnover organ. The Drosophila hindgut is comprised of three distinct segments: the diploid pylorus, the polyploid ileum, and the polyploid rectum. We have previously shown that ectopic expression of the pro-apoptotic genes hid and rpr causes cell death and regenerative hypertrophy in the pylorus. Here, we show that expression of hid and/or rpr does not activate a caspase sensor nor lead to cell death in the adult hindgut ileum or rectum. Polyploidy does not protect against cell death cues in these cell types, as ectopically expressing the caspase dronc (Caspase-9), often a downstream hid/rpr target, results in polyploid cell death. Surprisingly, the pylorus mostly resists cell death following dronc overexpression, which suggests that dronc expression alone is insufficient to kill pyloric cells. However, cell death in the pylorus depends on the canonical hid/rpr/dronc cell death pathway, as reducing the amount of dronc or increasing the levels of the dronc inhibitor diap1 reduces hid-mediated cell death and regeneration in the pylorus. Collectively, these data suggest that canonical death signaling is active in the regenerative pylorus, but distinct sensitivities to specific nodes of apoptotic regulation are present in each hindgut segment. We then compared our results to apoptotic gene expression in two other regenerative tissues: the larval eye and the adult midgut (both polyploid enterocytes and diploid enteroblasts). Both of these tissues behave like the regenerative pylorus. Specifically, hid/rpr overexpression robustly kills eye and midgut cells, while dronc overexpression does not. These data further underscore the distinct cell death signaling responses in the long-lived hindgut ileum and rectum. Finally, we find that the long-lived, hid/rpr-insensitive ileum and rectum lack a robust regenerative response to dronc killing, which may explain their distinct apoptotic responses. Our results argue that the Drosophila hindgut is an excellent model to reveal unique apoptotic regulation of long-lived epithelial tissues.