Programmed cell senescence is required for sensory organ development in Drosophila

Abstract

Cellular senescence is an irreversible cell-cycle arrest often associated with cancer and aging, yet its physiological role remains elusive. Here, we show developmentally programmed cellular senescence occurs in Drosophila imaginal epithelium. In developing wing discs, two clusters of cells exhibit hallmarks of cellular senescence such as elevated senescence-associated b-galactosidase activity, cell-cycle arrest, heterochromatinization, upregulation of a cyclin-dependent kinase (CDK) inhibitor Dacapo, cellular hypertrophy, Ras signaling activation, and upregulation of an inflammatory cytokine unpaired3, a possible component of the senescence-associated secretory phenotype. Blocking programmed cell senescence by inhibiting Ras signaling or its downstream transcription factor Pointed (Pnt) results in loss of sensory organ campaniform sensilla. Ras-Pnt signaling causes programmed cell senescence through a transcription factor Zfh2, thereby contributing to campaniform sensilla formation via the achaete-scute complex. Our observations uncover the evolutionary conservation of programmed cell senescence in invertebrates, which is required for the induction of the proper number of sensory organs.