Die or eat your neighbors: Induction of apoptosis or phagocytic activity in epithelial cells is a consequence of who dies first

Apoptosis is executed by the action of caspase proteases, which when activated above a lethal threshold, lead to a cell death and rapid clearance by professional (macrophages) or non-professional (neighboring cells) phagocytes. Phagocytosis of apoptotic cells involves recognition of the dying cell, internalization into phagosomes, and final degradation following fusion of the phagosomes with lysosomes. While macrophages are cells specialized in clearing apoptotic cells and other large particles, some nurse cells are also capable of acquiring a phagocytic activity, such as glia and Sertoli cells that clear dying neurons and germ cells, respectively. However, much less is known about how some cells within a tissue composed of similar cells are selected to acquire phagocytic properties. Here, I present our unpublished data about the mechanisms involved in the acquisition of phagocytic activity in a simple tissue of largely homogenous epithelial cells experiencing an identical stress. We show that following ionizing irradiation, some epithelial cells within the Drosophila wing imaginal discs do not die, but become positive to Lysotracker, a processes that requires the main phagocytic receptor Draper (CED-1 homolog). Indeed, while the cells still die in the absence of Draper, apoptotic clearance is severely impaired. Significantly, we also show that acquiring phagocytic activity requires a non-autonomous signal emanating from the dying adjacent cells. Overall, our data supports a model in which cells that stochastically first reached the lethal threshold of caspase activity, dictate survival and a phagocytic fate in neighboring cells that lag behind in reaching that threshold.