Notch Signaling during Organ of Corti Maturation and Maintenance

柯蒂器官成熟和维持过程中的Notch信号传导

基本信息

  • 批准号:
    10338132
  • 负责人:
  • 金额:
    $ 37.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-02-10 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

The majority of deafness and vestibular disorders occur due to loss or dysfunction of critical cells in the inner ear, including hair cells, supporting cells and neurons. Once lost or impaired, these cell types show little or no ability to regenerate in the mammalian inner ear. In recent years, there have been a number of exciting results regarding approaches to generate new hair cells in the endogenous epithelium, often through transformation of existing supporting cells. The Notch signaling pathway has been shown to be a key pathway in regulating the determination of the hair cell or supporting cell fate, through a process called lateral inhibition. In this system, cells expressing the Notch ligand activate Notch in the surrounding cells and prevent them from adopting a hair cell fate. This signaling creates the sensory mosaic in which each hair cell is surrounded by supporting cells. Inhibition of Notch can promote the conversion of supporting cells into hair cells, providing an avenue for replacing lost or dysfunctional hair cells. However, Notch signaling is a powerful pathway that often plays multiple roles during development. Our preliminary results indicate that in addition to cell fate choices, Notch also plays an essential role in cochlear maturation or maintenance via the JAG1 ligand. Specifically, our results demonstrate that JAG1 deletion does not cause cell fate alterations but instead leads to hearing deficits resembling auditory neuropathy in humans. We hypothesize that activation of Notch via the JAG1 ligand is required for aspects of sensory maturation and/or maintenance in the cochlea. The proposal outlined here aims to test this hypothesis, by (1) establishing the effects of deletion of Jag1 in the cochlear epithelium, (2) identifying the cell type and receptors that mediate JAG1 effects, and (3) establishing direct and indirect targets for JAG1-Notch1 signaling. Understanding the role of Notch signaling in postnatal maturation and sensory maintenance is essential for future regenerative therapies that rely on manipulating Notch signaling for hair cell replacement. .
大多数耳聋和前庭疾病是由于内部关键细胞的丢失或功能障碍引起的

项目成果

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Amy Kiernan其他文献

Amy Kiernan的其他文献

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{{ truncateString('Amy Kiernan', 18)}}的其他基金

Notch Signaling during Organ of Corti Maturation and Maintenance
柯蒂器官成熟和维持过程中的Notch信号传导
  • 批准号:
    10552025
  • 财政年份:
    2020
  • 资助金额:
    $ 37.58万
  • 项目类别:
Notch Signaling during Organ of Corti Maturation and Maintenance
柯蒂器官成熟和维持过程中的Notch信号传导
  • 批准号:
    9886922
  • 财政年份:
    2020
  • 资助金额:
    $ 37.58万
  • 项目类别:
Sensory Organ Formation in the Inner Ear
内耳感觉器官的形成
  • 批准号:
    8197187
  • 财政年份:
    2008
  • 资助金额:
    $ 37.58万
  • 项目类别:
Sensory Organ Formation in the Inner Ear
内耳感觉器官的形成
  • 批准号:
    8374113
  • 财政年份:
    2008
  • 资助金额:
    $ 37.58万
  • 项目类别:
Sensory Organ Formation in the Inner Ear
内耳感觉器官的形成
  • 批准号:
    7744629
  • 财政年份:
    2008
  • 资助金额:
    $ 37.58万
  • 项目类别:
Sensory Organ Formation in the Inner Ear
内耳感觉器官的形成
  • 批准号:
    7583056
  • 财政年份:
    2008
  • 资助金额:
    $ 37.58万
  • 项目类别:
Sensory Organ Formation in the Inner Ear
内耳感觉器官的形成
  • 批准号:
    9025772
  • 财政年份:
    2008
  • 资助金额:
    $ 37.58万
  • 项目类别:
Sensory Organ Formation in the Inner Ear
内耳感觉器官的形成
  • 批准号:
    7991778
  • 财政年份:
    2008
  • 资助金额:
    $ 37.58万
  • 项目类别:
Notch Signaling in Ear Development
耳朵发育中的Notch信号传导
  • 批准号:
    6608789
  • 财政年份:
    2002
  • 资助金额:
    $ 37.58万
  • 项目类别:
Notch Signaling in Ear Development
耳朵发育中的Notch信号
  • 批准号:
    6584457
  • 财政年份:
    2002
  • 资助金额:
    $ 37.58万
  • 项目类别:

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