Summary
Changes to the structure and function of neural networks are thought to underlie the evolutionary adaption of animal behaviours. Among the many development phenomena that generate changes, patterned programmed cell death is thought to play a role. For example, apoptotic cell death is the final fate of 40% of neurons in the developing Drosophila central nervous system. Outside the brain, modifications in the patterning of cell death are known to underlie the adaptation of tissue structure and function. However, whether similar modifications also underlie adaptive changes in neural circuitry remains unknown. Here we show that programmed cell death occurs continuously throughout fly neurogenesis, is stereotyped, happens very soon after neurons are born, and is thus a major force sculpting the architecture of neural networks. Blocking cell death permits the emergence of ‘undead’ neurons which elaborate complex processes into the neuropil and express distinct transmitter phenotypes. Thermogenetic activation of ‘undead’ neurons drives locomotion, demonstrating that they are functional. In vivo recordings of ‘undead’ neural activity in behaving animals demonstrates their integration into motor networks. Together, these data suggest that the evolutionary modulation of death-based patterning could be used to generate novel network motifs. Consistent with this, a comparative analysis of homologous neuronal populations in flightless dipterans reveals that altered patterns of cell death coincide with the loss of flight.