Junctional E-cadherin/p120-catenin Is Correlated with the Absence of Supporting Cells to Hair Cells Conversion in Postnatal Mice Cochleae.
Junctional E-cadherin/p120-catenin Is Correlated with the Absence of Supporting Cells to Hair Cells Conversion in Postnatal Mice Cochleae.
复制标题
E-钙粘蛋白/p120-连环蛋白的连接与出生后小鼠耳蜗中支持细胞向毛细胞转化的缺乏相关
DOI：
10.3389/fnmol.2018.00020
复制
发表时间：
2018
影响因子：
4.8
通讯作者：
Yang JM
中科院分区：
文献类型：
--
作者：
Luo WW;Wang XW;Ma R;Chi FL;Chen P;Cong N;Gu YY;Ren DD;Yang JM
众所周知，Notch 抑制会产生多余的毛细胞 (HC)，但会牺牲哺乳动物内耳中的支持细胞 (SC)。然而，随着动物年龄的增长，Notch 活性的抑制在诱导出生后耳蜗和平衡器官中 SC 向 HC 转化方面的效果逐渐减弱。有人提出，SC 到 HC 的转化能力与出生后哺乳动物椭圆囊中 E-钙粘蛋白的积累呈负相关。然而，E-钙粘蛋白的定位是否与哺乳动物内耳中 SC 到 HC 的转化能力之间的关系尚不清楚。在本研究中，我们从出生后第 0 天 (P0) 开始用 Notch 信号抑制剂 DAPT 治疗耳蜗，观察到明显的 SC 向 HC 转化以及感觉区域中的 E-钙粘蛋白/p120ctn 破坏。此外，SC 到 HC 的转化能力和 E-钙粘蛋白/p120ctn 解体在顶端很强，但向基部下降。我们进一步证明，即使在延长 DAPT 治疗后，HC 再生能力和 E-cadherin/p120ctn 破坏也会随着年龄的增长而降低，并在 P7 时停止。该时间与出生后耳蜗中 E-钙粘蛋白/p120ctn 的积累一致。这些结果表明，SC 转分化为 HC 的能力下降与出生后耳蜗中 E-钙粘蛋白/p120ctn 定位相关，这可能是哺乳动物耳蜗中缺乏 SC 向 HC 转化的原因。
Notch inhibition is known to generate supernumerary hair cells (HCs) at the expense of supporting cells (SCs) in the mammalian inner ear. However, inhibition of Notch activity becomes progressively less effective at inducing SC-to-HC conversion in the postnatal cochlea and balance organs as the animal ages. It has been suggested that the SC-to-HC conversion capacity is inversely correlated with E-cadherin accumulation in postnatal mammalian utricles. However, whether E-cadherin localization is linked to the SC-to-HC conversion capacity in the mammalian inner ear is poorly understood. In the present study, we treated cochleae from postnatal day 0 (P0) with the Notch signaling inhibitor DAPT and observed apparent SC-to-HC conversion along with E-cadherin/p120ctn disruption in the sensory region. In addition, the SC-to-HC conversion capacity and E-cadherin/p120ctn disorganization were robust in the apex but decreased toward the base. We further demonstrated that the ability to regenerate HCs and the disruption of E-cadherin/p120ctn concomitantly decreased with age and ceased at P7, even after extended DAPT treatments. This timing is consistent with E-cadherin/p120ctn accumulation in the postnatal cochleae. These results suggest that the decreasing capacity of SCs to transdifferentiate into HCs correlates with E-cadherin/p120ctn localization in the postnatal cochleae, which might account for the absence of SC-to-HC conversion in the mammalian cochlea.
登录
查看更多内容
影响因子：
7.2
作者：
Cavey, Matthieu;Lecuit, Thomas
通讯作者：
Lecuit, Thomas
影响因子：
5.3
作者：
Burns, Joseph C.;Corwin, Jeffrey T.
通讯作者：
Corwin, Jeffrey T.
影响因子：
56.9
作者：
FORGE, A;LI, L;NEVILL, G
通讯作者：
NEVILL, G
影响因子：
5.1
作者：
Gao, Zhen;Kelly, Michael C.;Chen, Ping
通讯作者：
Chen, Ping
影响因子：
56.9
作者：
CORWIN, JT;COTANCHE, DA
通讯作者：
COTANCHE, DA