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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Autores principales:	Xiang Chen, Yuwen Huang, Pan Gao, Yuexia Lv, Danna Jia, Kui Sun, Yunqiao Han, Hualei Hu, Zhaohui Tang, Xiang Ren, Mugen Liu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	zebrafish <i>mafba</i> cell proliferation cell differentiation ion homeostasis inner-ear development Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6c0a53ae4aa84d7fad47c93bfed74606
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spelling	oai:doaj.org-article:6c0a53ae4aa84d7fad47c93bfed746062021-11-25T16:50:57ZKnockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells10.3390/biomedicines91116992227-9059https://doaj.org/article/6c0a53ae4aa84d7fad47c93bfed746062021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1699https://doaj.org/toc/2227-9059Zebrafish 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.Xiang ChenYuwen HuangPan GaoYuexia LvDanna JiaKui SunYunqiao HanHualei HuZhaohui TangXiang RenMugen LiuMDPI AGarticlezebrafish<i>mafba</i>cell proliferationcell differentiationion homeostasisinner-ear developmentBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1699, p 1699 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	zebrafish <i>mafba</i> cell proliferation cell differentiation ion homeostasis inner-ear development Biology (General) QH301-705.5
spellingShingle	zebrafish <i>mafba</i> cell proliferation cell differentiation ion homeostasis inner-ear development Biology (General) QH301-705.5 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
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.
format	article
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
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_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_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_sort	knockout of <i>mafba</i> causes inner-ear developmental defects in zebrafish via the impairment of proliferation and differentiation of ionocyte progenitor cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6c0a53ae4aa84d7fad47c93bfed74606
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Knockout of <i>mafba</i> Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells

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