Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons

Elife. 2015 Aug 24;4:e07830. doi: 10.7554/eLife.07830.


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.

Keywords: Neuropilin; Semaphorin; auditory; axon guidance; cochlea; developmental biology; mouse; neuroscience; spiral ganglion neurons; stem cells.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Communication*
  • Cells, Cultured
  • Cochlea / embryology*
  • Hair Cells, Auditory, Inner / physiology*
  • Immunohistochemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Neurons / physiology*
  • Neuropilin-2 / metabolism*
  • Organ Culture Techniques
  • Spiral Ganglion / physiology*
  • Time-Lapse Imaging


  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neuropilin-2
  • Sema3f protein, mouse