During development, axons navigate to their appropriate targets in response to axon guidance cues and the fine-tuning of cell–cell adhesion. Post development, it is assumed that specific molecular programmes then help to maintain appropriate connections throughout the lifespan of the organism.
Nevertheless, mature neurons persist in expressing axon guidance proteins even after they have reached their targets. The function of these proteins in sustaining neuronal connections beyond the developmental stage remains largely unexplored. In this study (Vaikakkara Chithran et al., 2024), O'Connor and colleagues demonstrate that Fasciclin 3 (Fas3), a cell adhesion protein involved in axon guidance, is necessary for maintenance of the olfactory circuit in adult Drosophila. The authors show that Fas3 is widely expressed in the adult Drosophila central nervous system, with particular enrichment in a subset of olfactory neurons known as local interneurons in the olfactory lobes. In addition, knocking down the expression of Fas3 in these cells activates caspase-3, resulting in death of the olfactory circuit neurons and reduced survival of adults. This neuronal death can be rescued by overexpression of p35, an inhibitor of the apoptotic pathway. Thus, in addition to revealing a novel role for Fas3 in maintaining adult neuronal circuits and promoting the survival of adult Drosophila, this study highlights the critical function of axon guidance proteins in sustaining neuronal circuits beyond developmental stages.
