The Atoh1 expression levels are correlated with the arrangement, ciliary morphology, and electrophysiological characteristics of ectopic hair cell-like cells
The Atoh1 expression levels are correlated with the arrangement, ciliary morphology, and electrophysiological characteristics of ectopic hair cell-like cells
复制标题
Atoh1表达水平与异位毛细胞样细胞的排列、纤毛形态和电生理特征相关
DOI：
10.1016/j.neulet.2020.134758
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发表时间：
2020-01
影响因子：
2.5
通讯作者：
Juanmei Yang
中科院分区：
文献类型：
--
作者：
Yu Zheng;Wenwei Luo;Rui Ma;Ning Cong;Dongdong Ren;Fanglu Chi;Juanmei Yang
已有报道认为，Atoh1的表达水平和持续时间与毛细胞在发育过程中的存活、排列和立体纤毛束相关形态相关，但Atoh1的表达水平是否与新形成毛细胞的排列、束形成和电生理特性相关尚不清楚。为了解决这个问题，用不同滴度的编码Atoh1和/或EGFP的人腺病毒血清5型（Ad5）载体（EGFP-Atoh1+/-）处理新生大鼠耳蜗外植体。结果表明，较高的egfp - atoh11浓度导致较高的初始atoh1mrna表达水平，并诱导较小上皮脊（LER）中更多的异位毛细胞样细胞（ehclc）。此外，ehclc数量的逐渐增加与LER区域的逐渐转化有关，类似于毛细胞在发育过程中的转化。在高Atoh1表达的ehclc中，部分纤毛的排列方式与正常毛束相似。膜片钳记录显示，高Atoh1表达与ih电流细胞比例显著降低、瞬时钾通道电流比例显著降低、钾通道电流平均振幅显著增加相关，表明高Atoh1表达的ehclc比低Atoh1表达的ehclc成熟。综上所述，有证据表明，Atoh1的表达水平不仅影响毛细胞的排列和纤毛形态，还影响Atoh1诱导的ehclc的电生理特性，这些发现为今后针对耳聋的治疗提供了重要的指导。
Previous reports have suggested that the level and duration of Atoh1 expression are correlated with the survival, arrangement and stereociliary bundle-related morphology of hair cells during development, but whether Atoh1 expression levels are correlated with the arrangement, bundle formation and electrophysiological characteristics of newly formed hair cells is unknown. To address this question, cultured cochlear explants obtained from neonatal rats were treated with different titers of a human adenovirus serotype 5 (Ad5) vector encoding Atoh1 and/or EGFP (EGFP-Atoh1+/-). The results showed that higherEGFP-Atoh1concentrations led to higher initial Atoh1 mRNA expression levels and induced greater numbers of ectopic hair cell-like cells (EHCLCs) in the lesser epithelial ridge (LER). Furthermore, gradual increases in the number of EHCLCs were associated with the progressive conversion of the LER region similarly to that of hair cells during development. Some of the cilia on EHCLCs with higher Atoh1 expression were regularly arranged in a manner similar to that of normal hair bundles. As demonstrated through patch clamp recordings, high Atoh1 expression was associated with significantly decreased proportions of cells with Ihcurrents, significantly reduced proportions of transient potassium channel currents, and potassium channel currents with a greatly increased mean amplitude, which indicated that EHCLCs with high Atoh1 expression were more mature than those with low Atoh1 expression. Overall, the evidence suggests that the Atoh1 expression levels affect not only the arrangement and ciliary morphology of hair cells but also the electrophysiological characteristics of Atoh1-induced EHCLCs, and these findings provide important guidance for future therapies aimed at treating deafness.
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影响因子：
25
作者：
Zheng, JL;Gao, WQ
通讯作者：
Gao, WQ
影响因子：
64.8
作者：
Gubbels, Samuel P.;Woessner, David W.;Mitchell, John C.;Ricci, Anthony J.;Brigande, John V.
通讯作者：
Brigande, John V.
影响因子：
56.9
作者：
Bermingham, NA;Hassan, BA;Zoghbi, HY
通讯作者：
Zoghbi, HY
DOI：
10.1523/jneurosci.23-11-04395.2003
发表时间：
2003-06
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
K. Kawamoto;S. Ishimoto;R. Minoda;D. Brough;Y. Raphael
通讯作者：
K. Kawamoto;S. Ishimoto;R. Minoda;D. Brough;Y. Raphael
影响因子：
25
作者：
Woods, C;Montcouquiol, M;Kelley, MW
通讯作者：
Kelley, MW