Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons
Abstract
Auditory function is dependent on the formation of specific innervation patterns between mechanosensory hair cells and afferent spiral ganglion neurons (SGNs). In particular, type I SGNs must precisely connect with inner hair cells (IHCs) while avoiding connections with nearby outer hair cells (OHCs). The factors that mediate these patterning events are largely unknown. Using sparse-labeling and time-lapse imaging we visualized for the first time the behaviors of developing SGNs including active retraction of processes from OHCs, suggesting that some type I SGNs contact OHCs before forming synapses with IHCs. In addition, we demonstrate that expression of Semaphorin-3F in the OHC region inhibits type I SGN process extension by activating Neuropilin-2 receptors expressed on SGNs. These results suggest a model in which cochlear innervation patterns by type I SGNs are determined, at least in part, through a Semaphorin-3F-mediated inhibitory signal that impedes processes from extending beyond the IHC region.
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Animal experimentation: All animals used in this study were maintained in accordance with the NIH Animal Care and Use Committee, Protocol #1262, and the Georgetown University Animal Care and Use Committee, Protocol # 14-040-100179.
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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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