Adult expression of Semaphorins and Plexins is essential for motor neuron survival

Axon guidance cues direct the growth and steering of neuronal growth cones, thus guiding the axons to their targets during development. Nonetheless, after axons have reached their targets and established functional circuits, many mature neurons continue to express these developmental cues. The role of axon guidance cues in the adult nervous system has not been fully elucidated. Using the expression pattern data available on FlyBase, we found that more than 96% of the guidance genes that are expressed in the Drosophila melanogaster embryo continue to be expressed in adults. We utilized the GeneSwitch and TARGET systems to spatiotemporally knockdown the expression of these guidance genes selectively in the adult neurons, once the development was completed. We performed an RNA interference (RNAi) screen against 44 guidance genes in the adult Drosophila nervous system and identified 14 genes that are required for adult survival and normal motility. Additionally, we show that adult expression of Semaphorins and Plexins in motor neurons is necessary for neuronal survival, indicating that guidance genes have critical functions in the mature nervous system.