Genetic Regulation of Cochlear Development

项目总结 哺乳动物的内耳有六个专门负责听力和平衡的感觉器官。它们源自于 在发育中的内耳的独特位置出现的前感斑块，然后接受图案 使它们发育成前庭器官(眉骨和斑点)或Corti听觉器官的信号。 我们的实验室和其他人已经确定了驱动这些感应和模式事件的一些信号，例如 作为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 导致人类发育性耳部缺陷和听力障碍。然而，尽管取得了进展，但 虽然在理解耳朵中的这些信号方面取得了进展，但关于它们如何调节的根本问题仍然存在 感觉器官的诱导和构图。此外，很可能有许多其他基因和途径 对耳朵发育的调控仍有待确定。这项提案的目标是使用新的遗传工具和 单细胞转录组分析研究Notch和BMP作用机制的研究进展 信号产生内耳感觉器官并形成模式(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)。

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).