Notch Signaling in Ear Development
耳朵发育中的Notch信号传导
基本信息
- 批准号:6608789
- 负责人:
- 金额:$ 2.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-09-30 至 2004-01-23
- 项目状态:已结题
- 来源:
- 关键词:biological signal transduction developmental genetics ear hair cell gene expression gene interaction gene targeting genetic mapping genetically modified animals genome genotype histogenesis immunocytochemistry laboratory mouse labyrinth membrane proteins molecular cloning morphology nucleic acid sequence phenotype postdoctoral investigator quantitative trait loci receptor scanning electron microscopy
项目摘要
DESCRIPTION (provided by applicant): The mammalian inner ear is an exquisitely complex organ composed of a fluid-filled duct system punctuated by highly patterned sensory regions necessary for hearing and balance. Unfortunately, when damaged, the mammalian ear demonstrates little or no ability to regenerate these regions, making understanding their development an important prerequisite for the design of future therapies. This proposal seeks to test the role of one putative sensory gene, the Notch ligand Jagged 1 (Jag1). Notch signaling has previously been demonstrated to be important for hair cell and supporting cell differentiation by mediating lateral inhibition. However, it is clear from previous studies that Jag1 is unlikely to play a major role in lateral inhibition. This proposal will test the hypothesis that Jag1 is instead involved in sensory organ specification in the ear. A major impediment to understanding the role of Jag1 in ear development is that mice deleted for this gene die early during embryogenesis. In order to circumvent this problem, a conditional loss-of-function allele will be created using the Cre/loxP system. Preliminary data shows that there are modifier(s) in the C3H inbred mouse strain that cause ear defects in Jag1 + mice. Identifying genes that interact with Jag1 will further elucidate the role that this Notch ligand plays in ear development and potentially identify new genes involved in sensory specification in the ear. We propose to map and eventually clone these modifier(s). Data collected from these experiments will further our understanding of sensory field specification in the mammalian inner ear, providing a basis for eventually correcting environmental or genetic insults to these regions.
描述(由申请人提供):哺乳动物内耳是一个精致复杂的器官,由充满液体的管道系统组成,其中穿插着听觉和平衡所需的高度模式化的感觉区域。不幸的是,当受损时,哺乳动物的耳朵很少或没有能力再生这些区域,这使得了解它们的发育成为设计未来疗法的重要先决条件。这项提案旨在测试一个假定的感觉基因,Notch配体Jagged 1(Jag 1)的作用。Notch信号传导先前已被证明对于毛细胞和通过介导侧抑制支持细胞分化是重要的。然而,从以前的研究中可以清楚地看出,Jag 1不太可能在侧抑制中发挥重要作用。这项建议将测试的假设,Jag 1,而不是参与在耳朵的感觉器官规格。理解Jag 1在耳朵发育中的作用的一个主要障碍是,该基因缺失的小鼠在胚胎发育过程中早期死亡。为了避免这个问题,将使用Cre/loxP系统创建条件性功能丧失等位基因。初步数据显示,C3 H近交系小鼠品系中存在导致Jag 1+小鼠耳缺陷的修饰基因。识别与Jag 1相互作用的基因将进一步阐明这种Notch配体在耳朵发育中的作用,并可能识别参与耳朵感觉特异性的新基因。我们建议映射并最终克隆这些修改器。从这些实验中收集的数据将进一步了解哺乳动物内耳的感觉场规范,为最终纠正这些区域的环境或遗传损伤提供基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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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:
10338132 - 财政年份:2020
- 资助金额:
$ 2.03万 - 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:
10552025 - 财政年份:2020
- 资助金额:
$ 2.03万 - 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:
$ 2.03万 - 项目类别:
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