# Mouse vestibular regeneration and function

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $590,382

## Abstract

Abstract:
Sensory hair cells are required for balance function. Vestibular hair cell degeneration causes balance
dysfunction/hypofunction manifested as dizziness and vertigo. While the mammalian cochlea lacks the ability to
regenerate lost hair cells, a limited degree of spontaneous regeneration occurs in the utricle, a vestibular organ
detecting linear acceleration. Recent studies using fate-mapping techniques have pinpointed supporting cells as
precursors of regenerated hair cells. However, it is not clear whether regenerated hair cells are fully functional
and if organ function recovers. In preliminary experiments we have characterized hair cell degeneration and
regeneration in the mature mouse utricle and also a loss followed by recovery of vestibular evoked potentials
(VsEP) in vivo. The first aim of this proposal is to determine if increasing hair cell regeneration improves the
recovery of vestibular function. Specifically, regenerated hair cells labeled via fate-mapping are probed via
histology and electrophysiology to assess bundle morphology, mechanosensitvity, basolateral currents, and
synaptic properties including vesicle release. In parallel, VsEP responses are measured and compared to
histologic and electrophysiological measures. Next, by overexpressing Atoh1 via a transgenic approach, we will
study the histology and electrophysiology of Atoh1-overexpressing hair cells and also the overall VsEP
responses. In the second aim, we will determine if Atoh1 deletion prevents hair cell regeneration and the recovery
of VsEP responses. In parallel, fate-mapped, surviving hair cells will be examined for possible repair via histology
and electrophysiology. To gain an unbiased insight into the genetic signature of hair cell progenitors and surviving
hair cells, the third aim is designed to examine the damaged mature mouse utricle using single cell RNA
sequencing technologies. Here the first goal is to discover the genetic landscape of hair cell progenitors and
surviving hair cells in the damaged utricle. Secondly, we will examine the gene expression of the undamaged
and damaged utricle after Atoh1 overexpression. Lastly, we will use bioinformatic approaches to delineate the
trajectory of the spontaneous and Atoh1-enhaced supporting cell-hair cell transition and validate this
histologically. In summary, we will apply state-of-the art technologies (vestibular physiology, hair cell physiology,
single cell RNA-seq, bioinformatic strategies) to study vestibular hair cell regeneration in transgenic mouse
models. We have assembled a team of experts who have worked together to collect promising preliminary data.
At the end of this 5-year proposal, we will have 1) determined the relationship between hair cell regeneration
and functional recovery and 2) revealed and temporally ordered novel genes during mammalian hair cell
regeneration.

## Key facts

- **NIH application ID:** 10058261
- **Project number:** 5R01DC016919-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Alan Gi-Lun Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $590,382
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058261

## Citation

> US National Institutes of Health, RePORTER application 10058261, Mouse vestibular regeneration and function (5R01DC016919-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10058261. Licensed CC0.

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