A non-autonomous function of the core PCP protein VANGL2 directs peripheral axon turning in the developing cochlea

Development. 2018 Jun 14;145(12):dev159012. doi: 10.1242/dev.159012.

Abstract

The cochlea is innervated by neurons that relay sound information from hair cells to central auditory targets. A subset of these are the type II spiral ganglion neurons, which have nociceptive features and contribute to feedback circuits providing neuroprotection in extreme noise. Type II neurons make a distinctive 90° turn towards the cochlear base to synapse with 10-15 outer hair cells. We demonstrate that this axon turning event requires planar cell polarity (PCP) signaling and is disrupted in Vangl2 and Celsr1 knockout mice, and that VANGL2 acts non-autonomously from the cochlea to direct turning. Moreover, VANGL2 is asymmetrically distributed at intercellular junctions between cochlear supporting cells, and in a pattern that could allow it to act directly as an axon guidance cue. Together, these data reveal a non-autonomous function for PCP signaling during axon guidance occurring in the tissue that is innervated, rather than the navigating growth cone.

Keywords: Axon guidance; Cochlea; Planar cell polarity; Spiral ganglion neuron; Vangl2.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism*
  • Cell Polarity / genetics
  • Hair Cells, Auditory, Outer / physiology*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nociception / physiology
  • Noise
  • Receptors, G-Protein-Coupled / genetics*
  • Spiral Ganglion / embryology
  • Spiral Ganglion / physiology*

Substances

  • Celsr1 protein, mouse
  • Ltap protein, mouse
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled