Hair cells of the inner ear and lateral-line system rely on specialized ribbon synapses to transmit sensory information to the central nervous system. The molecules required to assemble these synapses are not fully understood. We show that Nrxn3, a presynaptic adhesion molecule, is critical for ribbon-synapse maturation in hair cells. In both mouse and zebrafish models, the loss of Nrxn3 results in significantly fewer intact ribbon synapses. We show in zebrafish that initially, nrxn3 mutants have normal pre- and post-synapse numbers, but synapses fail to pair, leading to postsynapse loss. We also demonstrate that Nrxn3 subtly influences synapse selectivity in zebrafish lateral-line hair cells that detect anterior flow. A 60% loss of synapses in zebrafish nrxn3 mutants dramatically reduces pre- and post-synaptic responses. Despite fewer synapses, auditory responses in zebrafish and mice are unaffected. This work demonstrates that Nrxn3 is a critical and conserved molecule required for the maturation of ribbon synapses. Understanding how ribbon synapses mature is essential to generating novel therapies to treat synaptopathies linked to auditory or vestibular dysfunction.
Presynaptic Nrxn3 is essential for ribbon-synapse maturation in hair cells
These authors contributed equally to the work
Biologists @ 100 - join us in Liverpool in March 2025
We are excited to invite you to a unique scientific conference, celebrating the 100-year anniversary of The Company of Biologists, and bringing together our different communities. The conference will incorporate the Spring Meetings of the BSCB and the BSDB, the JEB Symposium Sensory Perception in a Changing World and a DMM programme on antimicrobial resistance. Find out more and register your interest to join us in March 2025 in Liverpool, UK.
Pathway to Independence Programme: our 2024 PI fellows
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Development is excited to host a webinar series showcasing the latest developmental biology and stem cell research. The webinars are chaired each month by a different Development Editor, who invites talks from authors of exciting new papers and preprints. Visit Development presents... on the Node to see which topics are coming up and to catch up on recordings of past webinars.
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Modelling Plant Stem Cells: Evolution, Development and Regeneration
Early-career researchers can now apply for a funded place for the Modelling Plant Stem Cells: Evolution, Development and Regeneration Workshop happening on 18-21 May 2025. This is a great opportunity that could enhance your career in various ways. Application deadline: Friday 15 November 2024.
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