Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells
Zebrafish is an excellent model for exploring the development of the inner ear. Its inner ear has similar functions to that of humans, specifically in the maintenance of hearing and balance. Mafba is a component of the Maf transcription factor family. It participates in multiple biological processes...
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MDPI AG
2021-11-01
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| author | Xiang Chen Yuwen Huang Pan Gao Yuexia Lv Danna Jia Kui Sun Yunqiao Han Hualei Hu Zhaohui Tang Xiang Ren Mugen Liu |
| author_facet | Xiang Chen Yuwen Huang Pan Gao Yuexia Lv Danna Jia Kui Sun Yunqiao Han Hualei Hu Zhaohui Tang Xiang Ren Mugen Liu |
| author_sort | Xiang Chen |
| collection | DOAJ |
| description | Zebrafish is an excellent model for exploring the development of the inner ear. Its inner ear has similar functions to that of humans, specifically in the maintenance of hearing and balance. Mafba is a component of the Maf transcription factor family. It participates in multiple biological processes, but its role in inner-ear development remains poorly understood. In this study, we constructed a <i>mafba</i> knockout (<i>mafba<sup>−/−</sup></i>) zebrafish model using CRISPR/Cas9 technology. The <i>mafba<sup>−/−</sup></i> mutant inner ear displayed severe impairments, such as enlarged otocysts, smaller or absent otoliths, and insensitivity to sound stimulation. The proliferation of p63<sup>+</sup> epidermal stem cells and dlc<sup>+</sup> ionocyte progenitors was inhibited in <i>mafba<sup>−/−</sup></i> mutants. Moreover, the results showed that <i>mafba</i> deletion induces the apoptosis of differentiated K<sup>+</sup>-ATPase-rich (NR) cells and H<sup>+</sup>-ATPase-rich (HR) cells. The activation of p53 apoptosis and G0/G1 cell cycle arrest resulted from DNA damage in the inner-ear region, providing a mechanism to account for the inner ear deficiencies. The loss of homeostasis resulting from disorders of ionocyte progenitors resulted in structural defects in the inner ear and, consequently, loss of hearing. In conclusion, the present study elucidated the function of ionic channel homeostasis and inner-ear development using a zebrafish Mafba model and clarified the possible physiological roles. |
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| last_indexed | 2024-03-10T05:41:18Z |
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| series | Biomedicines |
| spelling | doaj.art-6c0a53ae4aa84d7fad47c93bfed746062023-11-22T22:32:08ZengMDPI AGBiomedicines2227-90592021-11-01911169910.3390/biomedicines9111699Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor CellsXiang Chen0Yuwen Huang1Pan Gao2Yuexia Lv3Danna Jia4Kui Sun5Yunqiao Han6Hualei Hu7Zhaohui Tang8Xiang Ren9Mugen Liu10Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, 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, 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, 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, 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, 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, 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, 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, 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, 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, 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, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, ChinaZebrafish is an excellent model for exploring the development of the inner ear. Its inner ear has similar functions to that of humans, specifically in the maintenance of hearing and balance. Mafba is a component of the Maf transcription factor family. It participates in multiple biological processes, but its role in inner-ear development remains poorly understood. In this study, we constructed a <i>mafba</i> knockout (<i>mafba<sup>−/−</sup></i>) zebrafish model using CRISPR/Cas9 technology. The <i>mafba<sup>−/−</sup></i> mutant inner ear displayed severe impairments, such as enlarged otocysts, smaller or absent otoliths, and insensitivity to sound stimulation. The proliferation of p63<sup>+</sup> epidermal stem cells and dlc<sup>+</sup> ionocyte progenitors was inhibited in <i>mafba<sup>−/−</sup></i> mutants. Moreover, the results showed that <i>mafba</i> deletion induces the apoptosis of differentiated K<sup>+</sup>-ATPase-rich (NR) cells and H<sup>+</sup>-ATPase-rich (HR) cells. The activation of p53 apoptosis and G0/G1 cell cycle arrest resulted from DNA damage in the inner-ear region, providing a mechanism to account for the inner ear deficiencies. The loss of homeostasis resulting from disorders of ionocyte progenitors resulted in structural defects in the inner ear and, consequently, loss of hearing. In conclusion, the present study elucidated the function of ionic channel homeostasis and inner-ear development using a zebrafish Mafba model and clarified the possible physiological roles.https://www.mdpi.com/2227-9059/9/11/1699zebrafish<i>mafba</i>cell proliferationcell differentiationion homeostasisinner-ear development |
| spellingShingle | Xiang Chen Yuwen Huang Pan Gao Yuexia Lv Danna Jia Kui Sun Yunqiao Han Hualei Hu Zhaohui Tang Xiang Ren Mugen Liu Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells Biomedicines zebrafish <i>mafba</i> cell proliferation cell differentiation ion homeostasis inner-ear development |
| title | Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells |
| title_full | Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells |
| title_fullStr | Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells |
| title_full_unstemmed | Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells |
| title_short | Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells |
| title_sort | knockout of i mafba i causes inner ear developmental defects in zebrafish via the impairment of proliferation and differentiation of ionocyte progenitor cells |
| topic | zebrafish <i>mafba</i> cell proliferation cell differentiation ion homeostasis inner-ear development |
| url | https://www.mdpi.com/2227-9059/9/11/1699 |
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