PT - JOURNAL ARTICLE AU - Ismael Fernández-Hernández AU - Evan B. Marsh AU - Michael A. Bonaguidi TI - Mechanosensory neuron regeneration in adult <em>Drosophila</em> AID - 10.1101/812057 DP - 2020 Jan 01 TA - bioRxiv PG - 812057 4099 - http://biorxiv.org/content/early/2020/06/06/812057.short 4100 - http://biorxiv.org/content/early/2020/06/06/812057.full AB - Auditory and vestibular mechanosensory hair cells do not regenerate following injury or aging in the adult mammalian inner ear, inducing irreversible hearing loss and balance disorders for millions of people. Research on model systems showing replacement of mechanosensory cells can provide mechanistic insights into developing new regenerative therapies. Here, we developed lineage tracing systems to reveal, for the first time, the generation of mechanosensory neurons in the Johnston’s Organ (JO) of intact adult Drosophila, which are the functional counterparts to hair cells in vertebrates. New JO neurons develop cilia, express an essential mechano-transducer gene and target central brain circuitry. Furthermore, we identified self-replication of JO neurons as an unexpected mechanism of neuronal plasticity, which is enhanced upon treatment with experimental and ototoxic compounds. Our findings introduce a new platform to expedite research about mechanisms and compounds mediating mechanosensory cell regeneration, with implications for hearing and balance restoration in humans.SUMMARY STATEMENT Using refined lineage tracing and live imaging, we identified self-renewal of mechanosensory neurons in adult Drosophila, the functional counterparts to vertebrate hair cells, and their enhanced regeneration through pharmacological administration.Competing Interest StatementThe authors have declared no competing interest.