Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB

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Abstract

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 FACS-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.

Data availability

Sequencing data have been deposited in GSA under accession code CRA010747.All data generated or analysed during this study are included in the manuscript and supporting file.

The following data sets were generated

(2023) Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB
National Genomics Data Center, CRA010747.

https://ngdc.cncb.ac.cn/search/?dbId=gsa&q=CRA010747

Article and author information

Author details

Ling-Yun Zhou

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Chen-Xi Jin

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Wen-Xiao Wang

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Lei Song

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Jung-Bum Shin

Department of Neuroscience, University of Virginia, Charlottesville, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3047-0874
Ting-Ting Du

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University, Shanghai, China

For correspondence
tingtingdu_jei@163.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0333-8739
Hao Wu

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University, Shanghai, China

For correspondence
wuhao@shsmu.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5317-902X

Funding

National Natural Science Foundation of China (82000975)

Ting-Ting Du

Fundamental Research Program Funding of Ninth People's Hospital affiliated to Shanghai Jiao Tong university School of Medicine (JYZZ057)

Ting-Ting Du

Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases (14DZ2260300)

Hao Wu

Shanghai Municipal Science and Technology Major Project (21JC1404000)

Hao Wu

National Natural Science Foundation of China (81970872)

Hao Wu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The study protocol was approved by the Ethics Committee of Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital (Shanghai, China) (SH9H-2020-A682-1) All animal maintenance and experimental procedures were performed by the recommendations in the Guide for the Institutional Animal Care and Use Committee (IACUC) of Shanghai Jiao Tong University.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.