# Hair Bundle Proteins

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $599,920

## Abstract

Project Summary
This project’s long-term objective is to elucidate mechanisms that control hair-bundle development and function,
show how defects in these mechanisms cause deafness and vestibular disorders, and identify pathways that
could be modulate to ameliorate these syndromes. Because the ability to control bundle development may assist
in hair-cell regeneration strategies, our project aims to uncover the mechanisms a hair cell uses to regulate and
modulate steps in bundle growth. Although our past work focused on postnatal development of bundles of apical
inner hair cells (IHCs) from the mouse cochlea, here we expand our scope here to include embryonic
development, outer hair cells (OHCs), and hair cells from apex to base of the cochlea. In the first Aim, we will
collect (and share) datasets of stereocilia actin and key row-specific proteins for IHCs from mid cochlear regions
to the base and OHCs from apex to base. Our goal is to discern the broad developmental plan for cochlea
bundles, and to identify the steps that individual hair cells modulate to create the distinct arrangements of
stereocilia in these diverse bundles. In the second Aim, we will characterize the first stage of stereocilia growth,
stage II in Tilney’s categorization, by measuring stereocilia dimensions, determining locations and concentrations
of key proteins, and revealing the presence of interstereocilia links during embryonic development. Importantly,
we will use mouse mutants to determine roles for the tip-link cadherins CDH23 and PCDH15, as well as the
molecular motors MYO15A, MYO7A, MYO3A, and MYO3B. In the final Aim, we address how the pattern of
stereocilia arrangement on the hair cell’s apical surface is determined. Our hypothesis is that spacing is initially
set when stereocilia grow during stage II; as they are tightly packed together then with their spacing set by
stereocilia width, their pattern is set and stabilized by growth of the rootlets and their interconnections through
rootlet-rootlet filaments and the cuticular plate. Mice lacking ANKRD24, GRXCR2, MYO7A, or SPTAN1 have
substantially altered stereocilia packing in mature hair cells, suggesting that these four proteins—and likely many
others—participate in setting stereocilia spacing.

## Key facts

- **NIH application ID:** 10978396
- **Project number:** 2R01DC002368-29A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Peter Gordon Barr-Gillespie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $599,920
- **Award type:** 2
- **Project period:** 1994-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978396

## Citation

> US National Institutes of Health, RePORTER application 10978396, Hair Bundle Proteins (2R01DC002368-29A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10978396. Licensed CC0.

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