内耳毛细胞通过机械电信号发出并传递信息。在前庭系统中，毛细胞的丢失是平衡失调的常见原因。在近期研究中发现，虽然小鼠前庭毛细胞在受损后能够部分得到自发性再生，但其数量和功能恢复尚不完全。Wnt/b-catenin信号通路对众多器官及组织干细胞增殖及分化起着重要的调控作用。b-catenin调控着毛细胞Atoh1的表达，而后者又与毛细胞的发育紧密联系。前期研究中，高表达b-catenin能使耳蜗Lgr5细胞增殖并分化为毛细胞。从而揭示了该通路在毛细胞再生领域的重要研究价值。本课题尝试通过在新生鼠椭圆囊毛细胞发育阶段敲除b-catenin及在受损成年鼠椭圆囊内提高b-catenin两种方法，验证其对椭圆囊内毛细胞发育与再生的调控作用。从而进一步验证调控Wnt/b-catenin信号通路可使内耳增殖性再生毛细胞。

The cochlea and the vestibular organs use a small population of sensory hair cell (HCs) as mechano-electric transducers. Within the vestibular system, the loss of hair cells usually leads to the functional disability. Recent study found that the hair cells can initiate a spontaneous restricted regeneration after injury in mice utricle. In numerous kinds of organs and tissues, the Wnt/b-catenin pathway plays an important role in the stem cell proliferation and differentiation. B-catenin controls the expression of Atoh1 which is closely link with the hair cell development. Our previous study found that some of the Lgr5+ cells in the cochlear can proliferate and different to new hair cells after b-catenin signaling overexpression. This result revealed the Wnt pathway is important in inner ear hair cell regeneration. In this study, we will handle two parts of experiment to certificate that the Wnt pathway plays an important role in the hair cell development and regeneration in utricle, b-catenin down-regulation will inhibit the hair cell postnatal development and its up-regulation will induce proliferative hair cell regeneration after injury in adult mice. Completion of the proposed project will test and verify the feasibility of manipulation Wnt pathway to induce proliferative hair cell regeneration in the inner ear.