# Mechanisms of PCP signaling in axon guidance and cochlear innervation

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $474,887

## Abstract

Project Summary
The cochlea is innervated by spiral ganglion neurons, which relay sound information from sensory hair cells to
central auditory targets. Deafness due to acoustic trauma is associated with pathologies in both spiral ganglion
neurons and the hair cells which they innervate, and an important aspect of repairing the deafened cochlea is
coaxing spiral ganglion neurons to re-innervate their hair cell partners. It is generally anticipated that hair cell re-
innervation will require the reactivation of developmental mechanisms. Therefore, understanding early
developmental events is an important prerequisite for regeneration-based therapeutic strategies.
A subset of spiral ganglion neurons has nociceptive characteristics and are thus equipped to detect acoustic
trauma, which may be important for preserving function. These are the type II spiral ganglion neurons, which
constitute a minority of cochlear afferents but innervate all outer hair cells. The development of type II neurons
is unique and facilitates outer hair cell innervation because their peripheral axons project beyond the inner hair
cells. An important component of cochlear innervation is how the type II spiral ganglion neurons subsequently
make a distinct 90° turn towards the cochlear base to synapse with multiple outer hair cells. While many aspects
of outer hair cell innervation are unknown, our laboratories have found that two signaling pathways, planar cell
polarity (PCP) signaling and Eph/Ephrin signaling, are required for the 90° turn that directs the peripheral axon
towards the cochlear base. A similar phenotype occurs with loss of the transcription factor Prox1 suggesting that
a regulatory hierarchy controls cochlear innervation.
The goal of this research is to establish the relationship between these two signaling pathways by examining
each in detail and relative to each other. This includes experiments in Aim 1 to distinguish between alternative
mechanisms in which PCP proteins pattern the organ of Corti prior to innervation or signal directly to the growth
cone. Since the Ephrin receptor EphA7 is also required for axon turning, in Aim 2 we will determine if these
pathways are linearly organized or if they are parallel and redundant signals with each promoting turning.
Remarkably the EphA7 promoter contains putative Prox1 binding sites suggesting that these guidance
mechanisms may be transcriptionally regulated. This hypothesis will be tested further in Aim 3. While these
experiments are focused on developmental processes, we anticipate that these are events which must be
reenacted during hair cell re-innervation and repair, and therefore the proposed research will advance therapies
for repairing the deafened cochlea.

## Key facts

- **NIH application ID:** 10051909
- **Project number:** 1R01DC018040-01A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** MICHAEL R DEANS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,887
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051909

## Citation

> US National Institutes of Health, RePORTER application 10051909, Mechanisms of PCP signaling in axon guidance and cochlear innervation (1R01DC018040-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10051909. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*