Rhpn2 regulates the development and function of vestibular sensory hair cells through the RhoA signaling in zebrafish

Yubei Dai; Qianqian Li; Jiaju Deng; Sihang Wu; Guiyi Zhang; Yuebo Hu; Yuqian Shen; Dong Liu; Han Wu; Jie Gong

doi:10.1016/j.jgg.2025.04.006

Rhpn2 regulates the development and function of vestibular sensory hair cells through the RhoA signaling in zebrafish

doi: 10.1016/j.jgg.2025.04.006

Department of Clinical and Translational Research Center, Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, School of Life Science, Nantong Laboratory of Development and Diseases, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China

基金项目:

This study was supported by grants from the Natural Science Foundation of Jiangsu Province (BK20221377 and BK20220607), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (22KJB180023), the National Natural Science Foundation of China Grants (32200783, 32350017, and 92368104), and the Qing Lan Project of Jiangsu Province.

详细信息

通讯作者:
Dong Liu,E-mail:liudongtom@gmail.com

Han Wu,E-mail:wuhantdfy@ntu.edu.cn

Jie Gong,E-mail:jgong188@ntu.edu.cn

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出版历程
- 收稿日期: 2025-01-20
- 录用日期: 2025-04-10
- 修回日期: 2025-04-10
- 刊出日期: 2026-01-31

Rhpn2 regulates the development and function of vestibular sensory hair cells through the RhoA signaling in zebrafish

Department of Clinical and Translational Research Center, Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, School of Life Science, Nantong Laboratory of Development and Diseases, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China

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摘要

摘要: Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells (HCs). Identifying the underlying genes involved in the morphogenesis and development of HCs is crucial. Our current study highlights rhpn2, a member of rho-binding proteins, as essential for vestibular HC development. The rhpn2 gene is highly expressed in the crista and macula HCs. Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number, accompanied by vestibular dysfunction. Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants. Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab. Furthermore, co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA, validating the interaction of the two proteins. rhpn2 knockout leads to a decreased expression of rock2b, a canonical RhoA signaling pathway gene. Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants. This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway, providing a target for the treatment of balance disorders.
- Stereocilia /
- Balance disorder /
- RhoA signaling /
- Crista hair cell /
- Zebrafish
Abstract: Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells (HCs). Identifying the underlying genes involved in the morphogenesis and development of HCs is crucial. Our current study highlights rhpn2, a member of rho-binding proteins, as essential for vestibular HC development. The rhpn2 gene is highly expressed in the crista and macula HCs. Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number, accompanied by vestibular dysfunction. Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants. Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab. Furthermore, co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA, validating the interaction of the two proteins. rhpn2 knockout leads to a decreased expression of rock2b, a canonical RhoA signaling pathway gene. Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants. This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway, providing a target for the treatment of balance disorders.
- Stereocilia /
- Balance disorder /
- RhoA signaling /
- Crista hair cell /
- Zebrafish

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参考文献(52)

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Rhpn2 regulates the development and function of vestibular sensory hair cells through the RhoA signaling in zebrafish

doi: 10.1016/j.jgg.2025.04.006

通讯作者:
Dong Liu,E-mail:liudongtom@gmail.com

Han Wu,E-mail:wuhantdfy@ntu.edu.cn

Jie Gong,E-mail:jgong188@ntu.edu.cn

计量

Rhpn2 regulates the development and function of vestibular sensory hair cells through the RhoA signaling in zebrafish

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留言板

Rhpn2 regulates the development and function of vestibular sensory hair cells through the RhoA signaling in zebrafish

doi: 10.1016/j.jgg.2025.04.006

通讯作者: Dong Liu,E-mail:liudongtom@gmail.com Han Wu,E-mail:wuhantdfy@ntu.edu.cn Jie Gong,E-mail:jgong188@ntu.edu.cn

计量

出版历程

Rhpn2 regulates the development and function of vestibular sensory hair cells through the RhoA signaling in zebrafish

计量

出版历程

目录

通讯作者:
Dong Liu,E-mail:liudongtom@gmail.com

Han Wu,E-mail:wuhantdfy@ntu.edu.cn

Jie Gong,E-mail:jgong188@ntu.edu.cn