# Unraveling Cochlear Otic Mesenchyme Cells: The Role of Pou3f4 in Cochlear Development

> **NIH NIH F31** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $39,125

## Abstract

PROJECT SUMMARY
Hearing impairment is a growing healthcare issue, which can have a large impact on an individual’s quality of
life. The cochlea is made up of a large heterogenous group of cells, all working in harmony to convert mechanical
stimuli into electrical signals resulting in the perception of sound. One such cell type is the otic mesenchyme
cells, the most numerous cell type within the cochlea, which are essential for the maturation of normal hearing
in both human and mouse. Indeed, mutations in Pou3f4, a mesenchymal specific transcription factor, causes a
variety of defects in the developing cochlea, including complete loss of endocochlear potential, shortening of the
cochlear duct, and decreased survival and fasciculation of spiral ganglion neurons (SGNs). We have recently
discovered, using scRNA-seq, that otic mesenchyme cells are not a homogenous population, but can be
separated into 4 genetically unique subpopulations. We have also shown, using immunohistochemistry with
antibodies for CAR3 and TGFBI, that two of the four mesenchyme subpopulations are spatially distinct within
the cochlea, revealing Car3-postive otic mesenchyme cells are located within the lateral wall, surrounding the
stria vascularis, and Tgfbi-positive otic mesenchyme cells make up the spiral limbus, which is essential for SGN
pathfinding. Therefore, we hypothesize that the cochlear mesenchyme cells consist of several subpopulations
that are (a) spatially distinct and (b) regulate shared and unique downstream target genes. In order to test this
hypothesis, we have designed two aims: (1) Determine how the spatial distribution of the cochlear mesenchyme
subpopulations are changed in the absence of Pou3f4 and (2) Define the regional gene regulatory networks
downstream of Pou3f4 in otic mesenchyme cells. Using a well-established in vitro mouse model and a three-
pronged single-cell multi-omics approach, we will elucidate regulatory elements in each mesenchymal
subpopulation, leading to the discovery of not only genes necessary for otic mesenchyme maturation, but novel
genes essential for the development of key cochlear processes such as endocochlear potential. This proposal
is a steppingstone in developing a more complete understanding of cochlear maturation, and specifically
understanding the role of an understudied cell type crucial for normal hearing.

## Key facts

- **NIH application ID:** 10479799
- **Project number:** 5F31DC019513-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Kevin Patrick Rose
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,125
- **Award type:** 5
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10479799

## Citation

> US National Institutes of Health, RePORTER application 10479799, Unraveling Cochlear Otic Mesenchyme Cells: The Role of Pou3f4 in Cochlear Development (5F31DC019513-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10479799. Licensed CC0.

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