# The Role of Sox2 in the Formation and Maintenance of Sensory Regions in Inner Ear Development

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2022 · $41,637

## Abstract

PROJECT SUMMARY
Understanding the development of the inner ear is extremely important for human health. Inner ear sensory
organs contain mechanosensitive hair cells required for hearing and balance. Hair cells are killed by damage
from loud noises and certain ototoxic drugs. The mammalian inner ear has minimal regenerative capacity for
forming new hair cells, so when damage occurs it can cause permanent hearing loss. Beyond damage, there
are a variety of possible mechanisms resulting in reduced hearing, balance issues, or deafness occurring in
the global population. Understanding how the inner ear develops can provide insights into the failure of hair
cell regeneration in mammals and may reveal strategies to restore hearing in humans. The Notch signaling
pathway and specifically the pluripotency factor Sox2 play important roles in inner ear development. Sox2, as a
Notch downstream target, is expressed broadly during early inner ear development. However, as the ear
continues to develop, Sox2 expression becomes restricted to prosensory domains, regions of the inner ear that
will later develop into auditory or vestibular sensory organs. The rest of the embryonic inner ear will form
nonsensory structures such as the semicircular canals. Data from our lab suggests that Sox2 expression is
present in both prosensory and nonsensory progenitors during early inner ear development but become
restricted to prosensory regions over time. The aim of this study is to understand the role of Sox2 during early
inner ear development. To test our hypothesis that the developmental potential of Sox2-expressing progenitor
cells changes over time, we will use a cell lineage tracing method to test whether an individual Sox2-
expressing cell is capable of generating prosensory or nonsensory cells, or both. In parallel, we will test
whether transcriptional targets of Sox2 change over time during ear development. Using a Sox2-RFP reporter
mouse line developed in our lab, we will isolate Sox2-expressing cells and identify the targets of Sox2 by a
chromatin immunoprecipitation-based assay (CUT&RUN). We will combine this with transcriptomic studies
(RNA-seq) to analyze how Sox2 binding is changing and affecting the transcriptional output at early and late
time points of inner ear development. Combining the results of methods like CUT&RUN and RNAseq will help
us understand how Sox2 differentially targets genes over time, as well as how this affects the overall
transcriptome of the developing otocyst. Our work will reveal the functional shift of a key regulator of inner ear
development, gain a more specific understanding of how cells specify to become hair cells through
development, and identify new strategies to target cells for hair cell regeneration.

## Key facts

- **NIH application ID:** 10466224
- **Project number:** 1F31DC019848-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Joel Charles Nelson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,637
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466224

## Citation

> US National Institutes of Health, RePORTER application 10466224, The Role of Sox2 in the Formation and Maintenance of Sensory Regions in Inner Ear Development (1F31DC019848-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10466224. Licensed CC0.

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