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

Satish R. Ghimire, Evan M. Ratzan, and Michael R. Deans

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.

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