# Neural defects in zebrafish auditory/vestibular mutants

> **NIH NIH R56** · STANFORD UNIVERSITY · 2021 · $474,166

## Abstract

PROJECT SUMMARY
Approximately one quarter of patients with vertigo or dizziness have central vestibular disorders.
In addition, hearing loss or tinnitus can have central origins. Despite the prevalence of central
deficits in the auditory/vestibular system in patients, our understanding of central dysfunction at
the molecular or cellular level in vertebrates is lacking. Here, we propose to characterize a novel
class of zebrafish mutants that have central auditory/vestibular deficits to gain insights into this
understudied area of research. This proposal focuses on two mutants: raumschiff and starliner,
which were isolated from chemical mutagenesis screens for hearing and balance defects.
Unlike our previously characterized mutants, raumschiff and starliner mutants have normal
vestibular induced eye movements despite presenting with an obvious balance defect while
swimming or at rest. In addition, a defect in hearing is present in both mutants. We have
identified mutations in two genes: in starliner mutants, the split ends (spen) gene harbors a
nonsense mutation and in raumschiff we identified a missense mutation in vacuolar protein
sorting 4a (vps4a). RNAseq anaylsis of mutant and sibling transcripts indicate that both mutants
have striking misregulation of gene expression in the hindbrain and midbrain regions, yet their
development and gross brain morphology is normal. These results suggest that the defects are
functional in nature and may involve circuit level or synaptic changes. To gain a better
understanding of the central defects, we will take advantage of imaging whole fish expressing
relevant transgene markers and use newly developed methods for brain-wide imaging of cellular
responses to auditory and vestibular stimuli. These experiments will focus on the regions or cell
types where misregulation of gene expression is most prevalent. Collectively our studies will
enhance our understanding of the genes and regulatory networks involved in central function.

## Key facts

- **NIH application ID:** 10412441
- **Project number:** 1R56DC018857-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Teresa A Nicolson
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,166
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412441

## Citation

> US National Institutes of Health, RePORTER application 10412441, Neural defects in zebrafish auditory/vestibular mutants (1R56DC018857-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10412441. Licensed CC0.

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