Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in Zebrafish
<b>Background</b>: Alternative splicing is essential for the physiological and pathological development of the inner ear. Disruptions in this process can result in both syndromic and non-syndromic forms of hearing loss. DHX38, a DEAH box RNA helicase, is integral to pre-mRNA splicing reg...
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2024-12-01
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| author | Mengmeng Ren Xiang Chen Liyan Dai Jiayi Tu Hualei Hu Xiaohan Sun Jiong Luo Pei Li Yiyang Fu Yuejie Zhu Weiqiang Sun Zhaohui Tang Mugen Liu Xiang Ren Qunwei Lu |
| author_facet | Mengmeng Ren Xiang Chen Liyan Dai Jiayi Tu Hualei Hu Xiaohan Sun Jiong Luo Pei Li Yiyang Fu Yuejie Zhu Weiqiang Sun Zhaohui Tang Mugen Liu Xiang Ren Qunwei Lu |
| author_sort | Mengmeng Ren |
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| description | <b>Background</b>: Alternative splicing is essential for the physiological and pathological development of the inner ear. Disruptions in this process can result in both syndromic and non-syndromic forms of hearing loss. DHX38, a DEAH box RNA helicase, is integral to pre-mRNA splicing regulation and plays critical roles in development, cell differentiation, and stem cell maintenance. However, its specific role in inner ear development remains undefined. Here, we utilized a <i>dhx38</i> knockout zebrafish model to monitor the ear morphology and elucidate a crucial role for DHX38 in the development of the zebrafish inner ear. <b>Methods</b>: Bright-field morphological analysis and in situ hybridization were performed to observe ear morphology changes. Immunofluorescence and semi-quantitative RT-PCR were employed to test apoptotic cells and abnormal splicing. <b>Results</b>: The <i>dhx38<sup>-/-</sup></i> mutant zebrafish showed significant inner ear impairments, including decrescent otocysts, absent semicircular canal protrusion, and smaller otoliths. These structural abnormalities were accompanied by substantial DNA damage and p53-dependent apoptosis within the inner ear cells. Alternative splicing analysis showed that genes related to DNA damage repair and inner ear morphogenesis are abnormal in <i>dhx38</i> knockout mutants. In summary, we suggest that <i>dhx38</i> promotes cell survival during the inner ear development of zebrafish by ensuring the correct splicing of genes related to DNA damage repair. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
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| series | Biomedicines |
| spelling | doaj-art-30150041595c4ff5a58a5dc0fa33b8f12025-01-24T13:23:44ZengMDPI AGBiomedicines2227-90592024-12-011312010.3390/biomedicines13010020Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in ZebrafishMengmeng Ren0Xiang Chen1Liyan Dai2Jiayi Tu3Hualei Hu4Xiaohan Sun5Jiong Luo6Pei Li7Yiyang Fu8Yuejie Zhu9Weiqiang Sun10Zhaohui Tang11Mugen Liu12Xiang Ren13Qunwei Lu14Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaSection of Hematology and Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USAKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China<b>Background</b>: Alternative splicing is essential for the physiological and pathological development of the inner ear. Disruptions in this process can result in both syndromic and non-syndromic forms of hearing loss. DHX38, a DEAH box RNA helicase, is integral to pre-mRNA splicing regulation and plays critical roles in development, cell differentiation, and stem cell maintenance. However, its specific role in inner ear development remains undefined. Here, we utilized a <i>dhx38</i> knockout zebrafish model to monitor the ear morphology and elucidate a crucial role for DHX38 in the development of the zebrafish inner ear. <b>Methods</b>: Bright-field morphological analysis and in situ hybridization were performed to observe ear morphology changes. Immunofluorescence and semi-quantitative RT-PCR were employed to test apoptotic cells and abnormal splicing. <b>Results</b>: The <i>dhx38<sup>-/-</sup></i> mutant zebrafish showed significant inner ear impairments, including decrescent otocysts, absent semicircular canal protrusion, and smaller otoliths. These structural abnormalities were accompanied by substantial DNA damage and p53-dependent apoptosis within the inner ear cells. Alternative splicing analysis showed that genes related to DNA damage repair and inner ear morphogenesis are abnormal in <i>dhx38</i> knockout mutants. In summary, we suggest that <i>dhx38</i> promotes cell survival during the inner ear development of zebrafish by ensuring the correct splicing of genes related to DNA damage repair.https://www.mdpi.com/2227-9059/13/1/20inner ear development<i>dhx38</i>zebrafishcell apoptosisDNA damage |
| spellingShingle | Mengmeng Ren Xiang Chen Liyan Dai Jiayi Tu Hualei Hu Xiaohan Sun Jiong Luo Pei Li Yiyang Fu Yuejie Zhu Weiqiang Sun Zhaohui Tang Mugen Liu Xiang Ren Qunwei Lu Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in Zebrafish Biomedicines inner ear development <i>dhx38</i> zebrafish cell apoptosis DNA damage |
| title | Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in Zebrafish |
| title_full | Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in Zebrafish |
| title_fullStr | Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in Zebrafish |
| title_full_unstemmed | Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in Zebrafish |
| title_short | Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in Zebrafish |
| title_sort | knockout of i dhx38 i causes inner ear developmental defects in zebrafish |
| topic | inner ear development <i>dhx38</i> zebrafish cell apoptosis DNA damage |
| url | https://www.mdpi.com/2227-9059/13/1/20 |
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