内耳精巧结构的发育极其复杂，发育异常可以引起内耳畸形。其中蜗神经发育不良患者人工耳蜗植入效果较蜗神经正常患者差。因此迫切需要寻找蜗神经发育不良的致病因素和相关基因，前期研究发现骨基质酸性蛋白DMP1可能与发病有关，并且 DMP1在内耳胚胎早期就有广泛表达。因此本课题旨在揭示DMP1在内耳发育中的作用机制。拟通过①体内实验：选用DMP1条件性敲除小鼠，选用不同组织特异性的cre酶转基因小鼠，在内耳不同部位和时间敲除特定细胞中的DMP1来观察表型改变；突变鼠增殖分化特点，细胞粘附表达特点；Wnt和 BMPs信号通路相关蛋白表达改变。②探讨机制，表型改变的小鼠前庭和耳蜗上皮体外培养，加入Wnt信号通路激活剂或抑制剂；BMPs信号通路抑制剂或外源性BMPs,探讨Wnt信号通路和BMPs信号通路调控DMP1参与内耳发育的机制。最终目的为了揭示DMP1基因在内耳发育中的新功能和作用机制。

The delicate structure of the inner ear is extremely complex. Dysplasia can cause inner ear malformation. The cochlear nerve dysplasia in patients with artificial cochlear implants effect is poor cochlear nerve normal patients.Thus it is urgent to find the cause of the cochlear nerve hypoplasia and related genes. Previous studies have found that bone matrix acidic protein DMP1 may be associated with disease,and DMP1 is widely expressed in early embryogenesis of the inner ear. So this topic aims to reveal the DMP1 role in the inner ear development mechanism. ①In Vivo, We explore the mechanisms of the DMP1 regulation based on temporal (different embryonic stages)and spatial(whole tissue、precursor cells、hair cells and supporting cells) control of DMP1 using the different Cre recombinase transgenic mice models. We observe the mutant mice phenotypes; proliferation characteristics of differentiation; expression of cell adhesion proteins; Wnt signaling pathways and BMPs signaling pathways related protein expression changes② In vitro (Mechanism exploration): we further validate whether Wnt and Bmps signaling pathways has synergistic effect with DMP1 involved in inner ear formation ,through in vitro culture of the vestibular and cochlear epithelium of the mutant mice adding the activator and inhibitor of the Wnt and BMPs signaling pathway .The ultimate aim is to reveal the new features and function of DMP1 gene in the inner ear development.