前庭毛细胞损伤是很多患者罹患眩晕的重要原因。非哺乳动物前庭毛细胞受损后能完全再生，但哺乳动物前庭毛细胞受损后仅表现为非常有限的再生。目前尚不清楚为什么哺乳动物前庭毛细胞缺乏完全的再生能力，也尚无有效方法使其完全再生。我们前期研究发现，Notch信号通路和Atoh1基因参与了哺乳动物前庭毛细胞的有限再生过程，但与非哺乳动物相比，Notch信号被抑制的程度和Atoh1的上调程度均明显低于非哺乳动物。因此，通过提高Notch信号被抑制和Atoh1上调的程度，将可能诱导哺乳动物前庭毛细胞充分再生。在本研究中，我们将采用Notch信号抑制剂LY411575以抑制Notch信号，同时应用含Tet-on系统的腺相关病毒载体AAV8-Atoh1以实现Atoh1可控性过表达，两者共同作用来诱导小鼠前庭毛细胞再生，并探讨毛细胞再生机制，为前庭毛细胞再生研究提供新策略，也为临床治疗眩晕提供新线索。

The impairment of vestibular hair cells (HCs) has been proven to be a significant cause for vertigo in numerous cases. The vestibular epithelium of non-mammalian vertebrates exhibits a capacity of complete HC regeneration after the lesion; however, the extent of vestibular HC regeneration in mammals is extremely limited. The reasons for the lack of effective regeneration mechanisms in the mammalian inner ear are unknown, and no effective approach is available to induce complete vestibular HC regeneration. Our previous studies reveal that Notch signaling and Atoh1 play important roles in the HC regeneration of mammalian vestibular epithelium. However, the levels of Notch inhibition and Atoh1 up-regulation is significantly lower than those in non-mammals. Therefore, we speculate that enhancing the levels of notch inhibition and Atoh1 up-regulation may induce complete vestibular HC regeneration in mammals. In the current study, we are planning to use a Notch inhibitor, LY411575, and a regulated Atoh1 over-expression system, AAV8-Atoh1, which is accomplished by an adenovirus-associated virus vector with the Tet-on components. And the mechanisms underlying vestibular HC regeneration will be also investigated. This study will be beneficial for the research of vestibular HC regeneration, and will serve as a new approach for the treatment of vertigo in the future.