Zebrafish myo7aa affects congenital hearing by regulating Rho-GTPase signaling

Binling Xie; Binling Xie; Binling Xie; Jiaxin Liang; Jiaxin Liang; Jiaxin Liang; Jifan Jiang; Jifan Jiang; Ting Zeng; Ting Zeng; Ling Liu; Ling Liu; Dinghua Xie; Ganghua Zhu; Lei Xiong; Lei Xiong; Lei Xiong; Kanjia Zhang; Dong Liu; Jie Gong; Xiangding Chen; Ruosha Lai; Huaping Xie

doi:10.3389/fnmol.2024.1405109

Frontiers in Molecular Neuroscience (Jul 2024)

Zebrafish myo7aa affects congenital hearing by regulating Rho-GTPase signaling

Binling Xie,
Binling Xie,
Binling Xie,
Jiaxin Liang,
Jiaxin Liang,
Jiaxin Liang,
Jifan Jiang,
Jifan Jiang,
Ting Zeng,
Ting Zeng,
Ling Liu,
Ling Liu,
Dinghua Xie,
Ganghua Zhu,
Lei Xiong,
Lei Xiong,
Lei Xiong,
Kanjia Zhang,
Dong Liu,
Jie Gong,
Xiangding Chen,
Ruosha Lai,
Huaping Xie

Affiliations

Binling Xie: Laboratory of Animal Nutrition and Human Health, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Binling Xie: State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Binling Xie: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China
Jiaxin Liang: Laboratory of Animal Nutrition and Human Health, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Jiaxin Liang: State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Jiaxin Liang: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China
Jifan Jiang: Laboratory of Animal Nutrition and Human Health, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Jifan Jiang: State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Ting Zeng: Laboratory of Animal Nutrition and Human Health, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Ting Zeng: State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Ling Liu: Laboratory of Animal Nutrition and Human Health, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Ling Liu: State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Dinghua Xie: Department of Otorhinolaryngology—Head & Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
Ganghua Zhu: Department of Otorhinolaryngology—Head & Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
Lei Xiong: Laboratory of Animal Nutrition and Human Health, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Lei Xiong: State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, Hunan, China
Lei Xiong: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China
Kanjia Zhang: Department of Otorhinolaryngology—Head & Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
Dong Liu: Nantong Laboratory of Development and Diseases, Key Laboratory of Neuroregeneration of Jiangsu and MOE, School of Life Sciences, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China
Jie Gong: Nantong Laboratory of Development and Diseases, Key Laboratory of Neuroregeneration of Jiangsu and MOE, School of Life Sciences, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China
Xiangding Chen: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China
Ruosha Lai: Department of Otorhinolaryngology—Head & Neck Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
Huaping Xie: Laboratory of Animal Nutrition and Human Health, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Science, Hunan Normal University, Changsha, Hunan, China

DOI: https://doi.org/10.3389/fnmol.2024.1405109
Journal volume & issue: Vol. 17

Abstract

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Introductionmyo7aa, the homolog of the human Usher 1B syndrome pathogenic gene, myo7A, plays an important role in stereociliary development and maintenance, therefore, is critical for hearing and balance. However, the molecular mechanisms that myo7aa regulate hearing and balance still need to be studied.MethodsIn this study, we generated two independent zebrafish myo7aa knockout lines using CRISPR/Cas9 technology. To investigate the effects of myo7aa on hearing, YO-PRO-1 staining and startle response assay were used. To gain insight into the specific molecular mechanisms by which myo7aa affects hearing, transcriptome sequencing and bioinformatics analysis were employed.ResultsOur study showed that hair cells of myo7aa-/- zebrafish can not take up YO-PRO-1 fluorescent dye and are insensitive to acoustic stimulation in myo7aa-/- zebrafish compared to wild type. Genes related to the Rho GTPase signaling pathway, such as arhgap33, dab2ip, and arghef40, are significantly down-regulated in myo7aa-/- zebrafish embryos at 3 dpf. GTP and ATP compensation can partially rescue the hair cell defects in myo7aa knockout zebrafish.DiscussionOur findings suggest that zebrafish myo7aa affects congenital hearing by regulating Rho GTPase signaling, and loss of myo7aa leads to abnormal Rho GTPase signaling and impairs hair cell function. myo7aa, myo7A, arhgap33, dab2ip, arghef40 and myo7aa-/- fonts in the abstract are italicized. -/- is a superscript format.

Published in Frontiers in Molecular Neuroscience

ISSN: 1662-5099 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.frontiersin.org/journals/molecular-neuroscience

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