人类感知声音的能力依赖于耳蜗听觉毛细胞，毛细胞包括内毛细胞和外毛细胞，分布于螺旋状耳蜗中，构成了耳蜗的频率拓扑结构。申请人前期的研究表明类维生素孤核受体-β基因（Rorb）在小鼠内耳中具有独特的表达模式：（1）在小鼠胚胎早期，Rorb基因首先表达在耳蜗顶端细胞中，呈现出顶端至底端的顺序表达模式；（2）小鼠内耳前庭毛细胞从未表达Rorb基因。因此，本项目致力于研究Rorb基因在内耳听觉系统发育中的功能。为了解答这一疑问，我们的策略是：分别构建Rorb基因敲除的小鼠和条件性过表达的小鼠，分析Rorb基因在内耳发育过程中的功能。本项目的研究促进了我们理解毛细胞早期发育分化和成年期发育成熟的分子机制，同时为耳鼻咽喉科临床上进行毛细胞损伤后再生提供了重要的理论依据。

Mechanosensory Hair cells (HCs) are the primary receptors of our sense of hearing, which contains inner hair cells (IHCs) and outer hair cells (OHCs). The special frequencies of Corti at different area along its longitudinal axis form the tonotopy. And, the expression of Rorb gene possess the apical to basal gradient in mouse cochlea and its expression is exclusive to the cochlear. This unique expression pattern of Rorb gene might play an important role in cochlear development. The funcion of Rorb gene will be tested through the Rorb deletion and overexpression mice model, which are generated using CRISPR/Cas9–mediated approach by oursevels. Taken together, our proposed study not only provide new insigts for the mechanisms uderling HC development and differenction, but also will provide fundations for how to regenrate new funcional HCs in clinic.