Loofah suppresses cell death in long-lived Drosophila hindgut enterocytes

ABSTRACT Tissue maintenance in the presence of cell death-promoting insults requires a host of molecular mechanisms. Many studies focus on cell renewal through regeneration, while fewer studies explore mechanisms that promote cell longevity despite cell death stimuli. Here, we reveal that the adult Drosophila hindgut ileum is an excellent model for studying tissue maintenance by long-lived cells. Hindgut ileal enterocytes resist the damaging detergent SDS and upstream caspase signaling by head-involution-defective (hid). This hid-induced death insensitivity arises early in adulthood and is associated with numerous transcriptional changes. We interrogated 82 of these transcriptional changes in a candidate screen for enhancers of hid-induced death in the ileum. Top among our screen hits is an immunoglobulin family cell adhesion gene, CG15312, that maintains the adhesion protein FasIII on cell membranes. In hid-expressing ileal cells, CG15312 loss causes cell death and pyknotic nuclear clustering. We name this conserved gene low on-membrane fas and enhancer of hid (loofah). Our findings reveal a new mechanism linking cell adhesion and cell death resistance in a long-lived cell type. Our work establishes a new model for studying tissue preservation.