Regenerative pathways in the avian cochlea

项目总结/摘要 30多年来，人们已经知道，通常静止的鸟类听觉器官中的支持细胞， 基底乳头，可以响应感觉毛细胞死亡与S期进入，有丝分裂，并产生 替代毛细胞这里提出的工作利用了几种方法的进步， 对氨基糖苷类抗生素诱导的免疫应答过程中基因表达的变化进行了全面、系统的清点， 毛细胞死亡和响应支持细胞。在多个时间点从单个细胞获得的初步数据 从鸡基底乳头感觉上皮分离的细胞显示， 蛋白酶激活受体2（PAR 2）是支持细胞和毛细胞进入S期的关键 再生该项目提出了一个具体的？c假设的激活途径，这将是明确的 并进行全面评估。此外，身份证？艾德？新再生途径的载体基因将被 在一个新的成年小鼠模型中评估长期毛细胞损失。在这里，重点是S阶段的进入， 小鼠椭圆囊和Corti器官支持细胞4周后氨基糖苷类诱导的毛细胞损失。 最后，该项目将集中在新再生的毛细胞的表征，通过重建的毛细胞。 新毛细胞成熟时发生的时间转录组变化。与此同时，建议 将转录组学数据与原位观察结果如毛束形成、平面细胞的变化 极性，突触连接的重建和电生理特征，如 机电转换和电调谐。

Project Summary / Abstract It is known for more than 30 years that supporting cells in the normally quiescent avian hearing organ, the basilar papilla, can respond to sensory hair cell death with S-phase entry, mitotic division, and generation of replacement hair cells. The work proposed here utilizes several methodological advances for an unbiased, comprehensive, and systematic inventorying of changes in gene expression during aminoglycoside-induced hair cell death and in responding supporting cells. Pilot data obtained at multiple time points from single cells isolated from the chicken basilar papilla sensory epithelium revealed that activation of a novel pathway linked to protease-activated receptor-2, PAR2, is essential for S-phase entry of supporting cells and hair cell regeneration. The project puts forward a speci?c hypothesis for the activation pathway, which will be explicitly and thoroughly evaluated. Moreover, the identi?ed e?ector genes for the novel regeneration pathway will be assessed in a new adult mouse model for long-term hair cell loss. Here, the focus is on S-phase entry of mouse utricle and organ of Corti supporting cells four weeks after aminoglycoside-induced hair cell loss. Finally, the project will focus on the characterization of newly regenerated hair cells by reconstructing the temporal transcriptomic changes that happen when the new hair cells mature. In parallel, it is proposed to align transcriptomic data with in situ observations such as hair bundle formation, changes in planar cell polarity, reestablishment of synaptic connections, and electrophysiological features such as mechanoelectrical transduction and electrical tuning.