Genetic Regulation of Cochlear Development

耳蜗发育的基因调控

• 批准号: 10304903
• 负责人: Andrew K Groves
• 金额: $ 62.29万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304903
• 关键词: Adult; Affect; Age-Months; Auditory; Cells; Cochlea; Cochlear duct; Collaborations; Communities; Crista ampullaris; Defect; Development; Dominant-Negative Mutation; Dose; Ear; Embryo; Environment; Equilibrium; Event; Failure; Functional disorder; Funding; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Goals; Hair Cells; Hearing; Hearing problem; Human; International; Knock-out; Knockout Mice; Labyrinth; Lateral; Lead; Location; Mediating; Medicine; Molecular; Morphology; Mosaicism; Mus; Mutagenesis; Mutate; NIH Mouse; Neurons; Organ; Organ of Corti; Paint; Pathway interactions; Pattern; Phase; Phenotype; Play; Regulation; Research; Resources; Role; Sensory; Signal Pathway; Signal Transduction; Specific qualifier value; Structure; Supporting Cell; Tamoxifen; Testing; To specify; Translating; United States National Institutes of Health; Work; bone morphogenetic protein receptor type I; cochlear development; college; deafness; ear development; gain of function; gamma secretase; hearing impairment; loss of function; macula; microCT; morphogens; mutant; notch protein; otoconia; progenitor; relating to nervous system; single-cell RNA sequencing; tool; transcriptome

PROJECT SUMMARY The mammalian inner ear contains six sensory organs specialized for hearing and balance. They derive from prosensory patches that arise at unique locations in the developing inner ear and then receive patterning signals that cause them to develop into vestibular organs (cristae and maculae) or the auditory organ of Corti. Our lab and others have identified some of the signals that drive these inductive and patterning events, such as the Notch, BMP, Fgf, and Shh pathways. It is increasingly clear that dysfunction of these pathways can also lead to developmental ear defects and hearing disorders in humans. However, despite the progress that has been made in understanding these signals in the ear, fundamental questions remain about how they regulate sensory organ induction and patterning. Moreover, it is likely that many other genes and pathways that regulate ear development have still to be identified. The goals of this proposal are to use new genetic tools and advances in single cell transcriptome analysis to understand the mechanism by which Notch and BMP signaling generate and pattern inner ear sensory organs (Aims 1 and 2), and to leverage existing resources at Baylor College of Medicine to search for new genes that regulate ear development and function (Aim 3).

项目概要 哺乳动物的内耳包含六个专门负责听觉和平衡的感觉器官。它们源自 前感觉斑块出现在发育中的内耳的独特位置，然后接受图案化 导致它们发育成前庭器官（嵴和斑）或柯蒂听觉器官的信号。 我们的实验室和其他人已经确定了一些驱动这些感应和模式事件的信号，例如 如 Notch、BMP、Fgf 和 Shh 通路。越来越清楚的是，这些途径的功能障碍也会 导致人类耳部发育缺陷和听力障碍。然而，尽管已经取得了进展 尽管已经了解了耳朵中的这些信号，但关于它们如何调节的基本问题仍然存在 感觉器官感应和模式化。此外，许多其他基因和途径可能 耳朵发育的调节仍有待确定。该提案的目标是使用新的遗传工具和 单细胞转录组分析的进展，以了解 Notch 和 BMP 的机制 信号生成和模式化内耳感觉器官（目标 1 和 2），并利用现有资源 贝勒医学院寻找调节耳朵发育和功能的新基因（目标 3）。