Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB.
Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB.
复制标题
作者：
Zhou LY;Jin CX;Wang WX;Song L;Shin JB;Du TT;Wu H
MRTF-SRF通路由于其在驱动参与各种细胞类型的肌动蛋白细胞骨架的大量基因的表达中的关键作用而被广泛研究。然而，MRTF-SRF在毛细胞中的具体贡献仍然未知。在这项研究中，我们发现，毛细胞特异性删除Srf或Mrtfb，但不是Mrtfa，导致类似的缺陷，在发展中的静纤毛尺寸和维护角质板的完整性。我们使用基于荧光激活细胞分选的毛细胞RNA-Seq分析来研究分别在Srf和Mrtfb突变体中观察到的变化的机制基础。有趣的是，转录组分析揭示了不同的配置文件的基因调控的Srf和Mrtfb，表明不同的转录调控机制的肌动蛋白细胞骨架活动介导的Srf和Mrtfb。在Srf突变体中使用腺相关病毒转导的外源性递送calponin 2部分地挽救了静纤毛尺寸和表皮板的F-actin强度的损伤，这表明Cnn 2作为Srf下游靶参与调节毛束形态和表皮板肌动蛋白细胞骨架组织。我们的研究首次揭示了毛细胞中Srf和Mrtfb介导的肌动蛋白细胞骨架的意外差异转录调节，并证明了SRF-CNN 2在调节静纤毛和表皮板的肌动蛋白动力学中的关键作用，为毛细胞发育和维持的分子机制提供了新的见解。
The MRTF–SRF pathway has been extensively studied for its crucial role in driving the expression of a large number of genes involved in actin cytoskeleton of various cell types. However, the specific contribution of MRTF–SRF in hair cells remains unknown. In this study, we showed that hair cell-specific deletion of Srf or Mrtfb, but not Mrtfa, leads to similar defects in the development of stereocilia dimensions and the maintenance of cuticular plate integrity. We used fluorescence-activated cell sorting-based hair cell RNA-Seq analysis to investigate the mechanistic underpinnings of the changes observed in Srf and Mrtfb mutants, respectively. Interestingly, the transcriptome analysis revealed distinct profiles of genes regulated by Srf and Mrtfb, suggesting different transcriptional regulation mechanisms of actin cytoskeleton activities mediated by Srf and Mrtfb. Exogenous delivery of calponin 2 using Adeno-associated virus transduction in Srf mutants partially rescued the impairments of stereocilia dimensions and the F-actin intensity of cuticular plate, suggesting the involvement of Cnn2, as an Srf downstream target, in regulating the hair bundle morphology and cuticular plate actin cytoskeleton organization. Our study uncovers, for the first time, the unexpected differential transcriptional regulation of actin cytoskeleton mediated by Srf and Mrtfb in hair cells, and also demonstrates the critical role of SRF–CNN2 in modulating actin dynamics of the stereocilia and cuticular plate, providing new insights into the molecular mechanism underlying hair cell development and maintenance.
表皮板的结构，一种体内肌动蛋白凝胶。
影响因子：
7.8
作者：
DeRosier, D J;Tilney, L G
通讯作者：
Tilney, L G
影响因子：
3.7
作者：
Olt J;Mburu P;Johnson SL;Parker A;Kuhn S;Bowl M;Marcotti W;Brown SD
通讯作者：
Brown SD