# Diversification of the mechanotransduction complex in vestibular hair cells

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $650,253

## Abstract

Abstract
The vestibular system utilizes specialized hair cells for sensing gravity and head motions. Vestibular hair cells
have been broadly characterized into two cell types: Type I and Type II. Clear differences also exist among the
zones of vestibular organs, consisting of a central zone surrounded by a peripheral zone of hair cells. How the
mechanotransduction machinery varies across these two cell types or zones is poorly understood. Existing
evidence suggests that the striolar (central) versus extrastriolar (peripheral) zones serve different functions such
as sensing high versus low frequencies. How these functional differences are achieved at the molecular level is
not clear. The aim of this proposal is to characterize the mechanotransduction complex in the different hair cells
and zones of the utricle, a vestibular organ that is vital for sensing gravity and head motions. We have preliminary
data that demonstrate differential expression of transcripts encoding a key component of the mechanotransduction
complex: transmembrane channel-like proteins (TMC1 and TMC2). In zebrafish and the mouse, both Tmc1 and
Tmc2 genes are expressed in regional gradients that correlate with the striolar and extrastriolar zones of the utricle.
We aim to determine the dynamic developmental and adult patterns of Tmc1/2 expression along with other
members of the mechanotransduction complex. We also intend to correlate these expression patterns with hair
bundle morphology and hair cell physiology. In addition, we will examine these features of TMC expression and
other components of the mechanotransduction complex in human utricular hair cells. Determining the extent of
conservation of these features among species will be essential for the interpretation of animal models and how
they inform approaches to regeneration of vestibular hair cells or other therapeutic methods for vestibular
dysfunction in human patients.

## Key facts

- **NIH application ID:** 10886798
- **Project number:** 5R01DC020879-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Alan Gi-Lun Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $650,253
- **Award type:** 5
- **Project period:** 2023-07-14 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886798

## Citation

> US National Institutes of Health, RePORTER application 10886798, Diversification of the mechanotransduction complex in vestibular hair cells (5R01DC020879-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10886798. Licensed CC0.

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