The Rho GTPase Cell Division Cycle 42 Regulates Stereocilia Development in Cochlear Hair Cells.
The Rho GTPase Cell Division Cycle 42 Regulates Stereocilia Development in Cochlear Hair Cells.
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DOI：
10.3389/fcell.2021.765559
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发表时间：
2021
影响因子：
5.5
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Du H;Zhou H;Sun Y;Zhai X;Chen Z;Wang Y;Xu Z
静纤毛是内耳毛细胞顶面上的肌动蛋白基细胞突起，在听觉和平衡感觉中起着关键作用。静纤毛的发育和维持受到严格的调节，这一过程中的缺陷通常会导致听力或平衡障碍。Rho GT3细胞分裂周期42（CDC 42）是肌动蛋白细胞骨架的关键调节因子。据报道，它定位于毛细胞静纤毛，并在静纤毛的维持中发挥重要作用。在本研究中，我们利用毛细胞特异性Cdc42基因敲除小鼠和CDC42抑制剂ML141来探讨CDC42在静纤毛发育中的作用。我们的数据表明，静纤毛的高度和宽度，以及静纤毛吸收的影响，Cdc42缺陷耳蜗毛细胞在出生后第8天（P8）检查。此外，ML141处理导致新生毛细胞中的平面细胞极性（PCP）缺陷。我们还表明，组成型活性突变体CDC42在耳蜗毛细胞的过度表达导致增强静纤毛发育缺陷。总之，目前的数据表明，CDC42在调节毛细胞静纤毛发育中起着关键作用。
Stereocilia are actin-based cell protrusions on the apical surface of inner ear hair cells, playing a pivotal role in hearing and balancing sensation. The development and maintenance of stereocilia is tightly regulated and deficits in this process usually lead to hearing or balancing disorders. The Rho GTPase cell division cycle 42 (CDC42) is a key regulator of the actin cytoskeleton. It has been reported to localize in the hair cell stereocilia and play important roles in stereocilia maintenance. In the present work, we utilized hair cell-specific Cdc42 knockout mice and CDC42 inhibitor ML141 to explore the role of CDC42 in stereocilia development. Our data show that stereocilia height and width as well as stereocilia resorption are affected in Cdc42-deficient cochlear hair cells when examined at postnatal day 8 (P8). Moreover, ML141 treatment leads to planar cell polarity (PCP) deficits in neonatal hair cells. We also show that overexpression of a constitutively active mutant CDC42 in cochlear hair cells leads to enhanced stereocilia developmental deficits. In conclusion, the present data suggest that CDC42 plays a pivotal role in regulating hair cell stereocilia development.
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细胞特异性转录组分析表明，成体支柱细胞和 Deiters 细胞表达耳蜗毛细胞特化的基因编码机制
影响因子：
4.8
作者：
Liu H;Chen L;Giffen KP;Stringham ST;Li Y;Judge PD;Beisel KW;He DZZ
通讯作者：
He DZZ
DOI：
10.1083/jcb.201704171
发表时间：
2017-11-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Avenarius MR;Krey JF;Dumont RA;Morgan CP;Benson CB;Vijayakumar S;Cunningham CL;Scheffer DI;Corey DP;Müller U;Jones SM;Barr-Gillespie PG
通讯作者：
Barr-Gillespie PG
DOI：
10.1523/jneurosci.3998-09.2009
发表时间：
2009-12-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Grimsley-Myers CM;Sipe CW;Géléoc GS;Lu X
通讯作者：
Lu X
DOI：
10.1073/pnas.2334417100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Belyantseva, IA;Boger, ET;Friedman, TB
通讯作者：
Friedman, TB
影响因子：
9.2
作者：
Manor, Uri;Disanza, Andrea;Grati, M'Hamed;Andrade, Leonardo;Lin, Harrison;Di Fiore, Pier Paolo;Scita, Giorgio;Kachar, Bechara
通讯作者：
Kachar, Bechara