title: 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 (HCs) and afferent spiral ganglion neurons (SGNs). In particular, type I SGNs must precisely connect with inner HCs (IHCs) while avoiding connections with nearby outer HCs (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.
authors: Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, Bethesda, United States.
authors: Thomas M
authors: TM
authors: Coate
authors: Department of Biology, Georgetown University, Washington, United States.
authors: Nathalie A
authors: NA
authors: Spita
authors: Department of Biology, Georgetown University, Washington, United States.
authors: Kaidi D
authors: KD
authors: Zhang
authors: Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, Bethesda, United States.
authors: Kevin T
authors: KT
authors: Isgrig
authors: Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, Bethesda, United States.
authors: Matthew W
authors: MW
authors: Kelley
mesh_terms: D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D003051:Cochlea / Q000196:embryology*; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D039943:Neuropilin-2 / Q000378:metabolism*; D009924:Organ Culture Techniques; D013136:Spiral Ganglion / Q000502:physiology*; D059008:Time-Lapse Imaging
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C491229:Sema3f protein, mouse
keywords: Neuropilin; Semaphorin; auditory; axon guidance; cochlea; developmental biology; mouse; neuroscience; spiral ganglion neurons; stem cells