# Development of an in vivo model system of sensory afferent neuron regeneration

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $427,625

## Abstract

Project Summary
The afferent neurons of the eighth cranial nerve transmit information from the cochlea and vestibular organs to
the brainstem. These neurons can be lost following damaging noise exposure, ototoxic injury, or as a
consequence of normal aging. Once lost, afferent neurons do not regenerate, and their depletion can result in
permanent hearing and balance deficits. In the case of hearing, clinical strategies to restore sensory function,
such as cochlear implants, require survival of a sufficient number of spiral ganglion neurons. Unfortunately,
there is currently no practicable method for replacing lost spiral ganglion neurons. Although the mammalian
cochlea lacks the ability to regenerate neurons, the spiral ganglion contains a population of cells that express
Nestin, which is widely regarded as a marker for neural stem cells. Studies conducted in mice have
demonstrated that these Nestin-expressing cells do not divide once the cochlea has matured, and the signaling
molecules that regulate their proliferation are not known. One factor that hinders the study of neurogenesis in
the cochlea is that the cell bodies of cochlear afferents and Nestin-expressing cells are housed within bone in
the inner ear and are not visually or experimentally accessible in living mammals. The task of developing
methods for neuronal replacement in the inner ear would be greatly facilitated by the introduction of an
appropriate model system to identify the basic cellular signals that permit ongoing addition and spontaneous
regeneration of afferent neurons. The objective of the present proposal is to establish the posterior lateral line
(pLL) ganglion of larval zebrafish as a model system for the study of neuronal repair and replacement. The pLL
ganglion is comprised of ~50 neurons, which can be easily visualized in living animals. Current data indicate
that about five new neurons/day are added to the pLL ganglion, but the identities of neural precursor cells and
the factors that regulate their proliferation are not known. We have found that cells in larval pLL ganglion
express two markers for neural precursors: Nestin and NeuroD. Moreover, expression of these two markers
occurs in spatially distinct regions, suggesting two domains within the pLL ganglion that possess progenitor
cells. Our studies will determine the contributions of each population to the process of ongoing neurogenesis in
the pLL ganglion and reveal whether proliferation of either (or both) cell types is enhanced following ablation of
a subset of afferent neurons. We will also quantify expression levels of Nestin and NeuroD within the ganglion
as function of age to define the contribution of each cell type to the process of neuronal addition and
regeneration. Finally, we will evaluate the function of macrophages in neurogenesis and regeneration of pLL
ganglion neurons. Experiments will determine whether macrophages are activated by neuronal injury and will
resolve whether they help promote th...

## Key facts

- **NIH application ID:** 11053154
- **Project number:** 1R21DC021762-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Lavinia Sheets
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,625
- **Award type:** 1
- **Project period:** 2024-09-19 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11053154

## Citation

> US National Institutes of Health, RePORTER application 11053154, Development of an in vivo model system of sensory afferent neuron regeneration (1R21DC021762-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11053154. Licensed CC0.

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