Genetic Regulation of Cochlear Development

项目摘要 哺乳动物的内耳包含六个专门用于听觉和平衡的感觉器官。它们源自 在发育中的内耳的独特位置出现的前感觉贴片，然后接收模式 这些信号导致它们发育成前庭器官（嵴和黄斑）或Corti听觉器官。 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化事件的信号，例如 如Notch、BMP、FGF和Shh通路。越来越清楚的是，这些通路的功能障碍也可以 导致人类发育性耳缺陷和听力障碍。然而，尽管取得了进展， 虽然我们对耳内这些信号的理解已经取得了进展，但关于它们如何调节的基本问题仍然存在。 感觉器官诱导和模式化。此外，很可能许多其他基因和途径， 调节耳朵发育的方法还有待于确定。该提案的目标是使用新的遗传工具， 单细胞转录组分析的进展，以了解Notch和BMP 信号产生和模式内耳感觉器官（目标1和2），并利用现有的资源， 贝勒医学院寻找新的基因，调节耳朵的发育和功能（目标3）。

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).