# Characterizing hair cell regeneration in the larval zebrafish inner ear

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Death of sensory hair cells in the inner ear is a common cause of auditory and vestibular dysfunction in
humans. This damage is permanent due to the inability of mammals to effectively regenerate inner ear sensory
patches beyond the neonatal stage. In contrast, non-mammalian vertebrate species such as birds and fish can
regenerate hair cells throughout life. This discrepancy in regeneration capacity between mammals and non-
mammalian vertebrates is not well understood. In species that can regenerate hair cells, the nonsensory
support cells that surround hair cells can act as hair cell progenitors. In vivo studies of inner ear hair cell
regeneration and support cells are limited by the inner ear’s location within the bony skull of mammals and
birds. As a result, the zebrafish lateral line, an external sensory system for detecting changes in water flow,
has been developed as an alternative model for studying support cells and hair cell regeneration in living
animals. However, the degree to which the mechanisms of regeneration in the lateral line are similar to those
of the ear is unclear. The zebrafish inner ear is an understudied system that has the potential to bridge the gap
between mammalian inner ear and lateral line studies. This project examines hair cell regeneration in the
zebrafish inner ear during the larval stage, at which point the sensory organs become fully functional and
remain accessible for in vivo imaging. We aim to identify hair cell precursors in the zebrafish inner ear and
determine when and how they give rise to new hair cells during regeneration. In the inner ear of birds and
mammals, support cells regenerate hair cells by proliferating and differentiating or by direct transdifferentiation.
In the zebrafish lateral line, only the former mechanism is used. In Aim 1 of this proposal, we will use a novel
method of hair cell ablation to determine the timecourse of regeneration and whether cell proliferation,
transdifferentiation, or both are used in the zebrafish inner ear. Hair cells in the lateral line are regenerated
primarily by a spatially and functionally distinct group of support cells. Whether a similar support cell subtype
exists in the zebrafish inner ear is unknown. In Aim 2, we will validate putative inner ear support cell subtypes
identified through single-cell RNA-seq analysis. We will then generate transgenic lines labeling support cell
subtypes and use fate mapping to identify hair cell precursors. Together these experiments will characterize
the timing and mechanism of hair cell regeneration and the diversity of support cell subtypes in the zebrafish
inner ear. This work will help to establish the zebrafish inner ear as an outstanding in vivo model system for
future in-depth studies of support cells and their roles in conserved mechanisms of regeneration. Expanding
our knowledge of the mechanisms of inner ear hair cell regeneration in animals such as the zebrafish will
ultimately lead to the adva...

## Key facts

- **NIH application ID:** 10604748
- **Project number:** 1F31DC020898-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Marielle Beaulieu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-09-16 → 2024-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10604748

## Citation

> US National Institutes of Health, RePORTER application 10604748, Characterizing hair cell regeneration in the larval zebrafish inner ear (1F31DC020898-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10604748. Licensed CC0.

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