内耳亚结构耳蜗和前庭皆具有独特的平面细胞极性(planar cell polarity)，研究表明耳聋的编码蛋白多定位于纤毛束，毛细胞纤毛正常的发育和规律的极性排列与听觉和平衡功能密切相关，Rab11a是重要的小G蛋白，参与多种胞内外物质运输，在体外细胞培养和蟾蜍中已被证实与纤毛发育和极性形成相关。我们前期研究表明Rab11a在内耳发育不同时期均有表达，Rab11a突变新生小鼠耳蜗毛细胞静纤毛变短、融合或消失，该现象以耳蜗内毛细胞为甚；前庭毛细胞静纤毛倒伏、紊乱，动纤毛变短或消失，极性分界线位置改变，耳蜗和前庭毛细胞表型呈现不一致，具体机制不明。本研究拟通过转基因小鼠体内和体外实验揭示Rab11a对内耳前庭和耳蜗毛细胞纤毛发育差异的具体机制，寻找毛细胞纤毛极性排列的重要调控基因，指导新生毛细胞纤毛极性重塑，探索毛细胞功能性再生的潜在机制。

A unique planar cell polarity exists in the inner ear. Studies have shown that proteins encoded by deafness genes are mostly localized to hair bundles, while the normal development of the hair cell stereocilia and the proper polarity arrangement are critical to the auditory functions. Rab11a is an important small G protein involved in a variety of intracellular and extracellular transport, and in cilia development and polarity formation demonstrated in cell culture and in bullfrogs. Our previous studies suggested that Rab11a was expressed in various stages of inner ear development. The stereocilia in the cochlear of Rab11a mutant mice were shortened, fused or disappeared, more severe for the stereocilia of inner hair cells. The vestibular stereocilia were disorganized and lack of erect projection, along with shorted or disappeared kinocilia. The position of the line of polarity reversal (LPR) also altered. As the distinct phenotypes were seen in the cochlea and in the vestibular organs, pertaining mechanism is yet known. This study aims to reveal the regulatory mechanism of Rab11a on the stereocilia development of the inner ear, using in vivo and in vitro approaches and using transgenic mice. The ultimate goal is to unravel the mechanism of stereocilia development and explore the potential mechanism of functional hair cell regeneration.