哺乳动物Corti's器的整体再生相关研究

Permanent sensorineural hearing loss is mainly caused by dysfunction of corti's organ. Research on hair cell regeneration is mainly stay at the cellular level. Functional corti's organ regeneration will be the effective solution for the treatment of deafness. It has been confirmed that cell adhesion factor and planar polarity protein play a key role for convergence and stretch of embryonic corti's organ. We also observed Math1-drive hair cells and supporting cells were in a similar convergence and stretch as developmental corti's organ. Based on our pilot studies, we propose the concept of the corti's organ regeneration, our goals include: 1) by using Ltap-GFP transgenic mice, p120 knockout mice and the planar cell polarity protein mutant mice to get the rules in convergence and stretch; 2) by multi-manipulate Sox2, Prox1, Math1 and Notch signaling level to adjust the number and proportion of the newly formed hair cells and supporting cells; 3) by regulating cell adhesion factor and planar cell polarity protein level to get the newly formed hair cells and supporting cells from disorder to order; 4) patch-clamp technique will be performed to detect the function of rearranged corti's organ

耳蜗corti's器的功能不全是永久性感音神性聋的根本原因。目前内耳毛细胞的再生研究主要在细胞水平上。而有功能的听器整体再生才是治疗耳聋的根本解决办法。本课题组在前期研究中证实了细胞粘附因子和平面极性蛋白对听器胚胎发育的汇聚伸展和规律重排发挥了重要作用；另外，在通过Math1诱导毛细胞再生的实验中观察到再生的毛细胞-支持细胞发生了汇聚现象和结构重排。基于此，本课题提出听器整体结构再生的概念，其研究内容主要包括：1）通过采用Ltap-GFP转基因小鼠、p120基因敲除小鼠和平面细胞极性蛋白突变小鼠研究汇聚伸展和平面极性的相关规律；2）通过多向调节Sox2,Prox1,Math1和Notch信号的水平，诱导再生毛细胞，再生支持细胞形成特定的数量和比例；3）通过调节细胞粘附因子和平面极性蛋白的水平诱导再生毛细胞-再生支持细胞发生从无序到有序的重排；4）膜片钳技术鉴定结构重排前后再生听器的功能变化

耳蜗corti’s器的功能不全是永久性感音神性聋的根本原因。目前内耳毛细胞的再生研究主要在细胞水平上。而有功能的听器整体再生才是治疗耳聋的根本解决办法。本课题组在前期研究中证实了细胞粘附因子和平面极性蛋白对听器胚胎发育的汇聚伸展和规律重排发挥了重要作用；另外，在通过Math1诱导毛细胞再生的实验中观察到再生的毛细胞-支持细胞发生了汇聚现象和结构重排。基于此，本课题提出听器整体结构再生的概念，研究内容主要包括：1）通过采用Ltap-GFP转基因小鼠、p120基因敲除小鼠和平面细胞极性蛋白突变小鼠耳蜗和前庭研究汇聚伸展和平面极性的相关规律；2）通过多向调节Math1水平和Notch信号通路，诱导耳蜗和前庭再生毛细胞，再生支持细胞形成特定的数量和比例；3）通过调节细胞粘附因子和平面极性蛋白及Wnt通路调控纤毛极性.