# The role of Notch signaling in the maintenance and function of cochlear sensory cells

> **NIH NIH F31** · UNIVERSITY OF ROCHESTER · 2021 · $46,036

## Abstract

Abstract.
The six sensory organs of the mammalian inner ear function to mediate hearing and balance. Mechanosensory
hair cells, supporting cells, and spiral ganglion neurons are three essential cell types that comprise the inner ear
sensory regions. Hearing loss is commonly caused by damage to these essential cell types which, in mammals,
lack the capacity to regenerate. Thus, identifying signaling pathways that are involved in the development and
maintenance of these cell types is of great importance. Notch has been shown to play two essential roles in
embryonic inner ear sensory development: 1) establishes the prosensory progenitors that give rise to hair cells
and supporting cells, and 2) mediates which cell fate is adopted by the sensory precursor, either hair cell or
supporting cell. Despite these important early roles, there is a limited understanding of the function of Notch
signaling postnatally. The Notch ligand Jagged1 (JAG1) has dynamic expression throughout inner ear
development, and is the only reported Notch ligand maintained into adulthood where it is expressed in supporting
cells.
Here, to understand the role of JAG1-Notch signaling in the postnatal inner ear we utilize a Cre/loxP
recombination system to conditionally delete either JAG1 or Notch receptors in supporting cells at postnatal day
(P)0/P1 and assess for effects on hearing and cochlear morphology. Preliminary results indicate that JAG1
signaling is required postnatally for normal hearing function, as Sox2-Jag1cko mice display a specific form of
hearing loss termed auditory neuropathy, that specifically affects the inner hair cell pathway. In Aim 1, we will
determine how JAG1 signaling functions in maturation and/or maintenance of the postnatal cochlea and test our
hypothesis that postnatal JAG1 signaling influences stereocilia morphogenesis and/or maintenance. In Aim 2,
we will identify the Notch receptor mediating the effects of JAG1 in the postnatal cochlea and test the hypothesis
that JAG1 signals through the Notch1 and/or Notch2 receptor(s) in postnatal cochlear supporting cells. Our
preliminary data suggests Notch1 may be the predominant JAG1 receptor as Sox2-Notch1cko mice show
profound deafness at 6-weeks of age. These studies will elucidate novel functions for JAG1-Notch signaling in
hearing maturation and/or maintenance in the postnatal cochlea.

## Key facts

- **NIH application ID:** 10146338
- **Project number:** 5F31DC018198-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Felicia Aileen Gilels
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146338

## Citation

> US National Institutes of Health, RePORTER application 10146338, The role of Notch signaling in the maintenance and function of cochlear sensory cells (5F31DC018198-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146338. Licensed CC0.

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