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基因敲除通过损害离子细胞祖细胞的增殖和分化导致斑马鱼内耳发育缺陷。

Knockout of Causes Inner-Ear Developmental Defects in Zebrafish via the Impairment of Proliferation and Differentiation of Ionocyte Progenitor Cells.

作者信息

Chen Xiang, Huang Yuwen, Gao Pan, Lv Yuexia, Jia Danna, Sun Kui, Han Yunqiao, Hu Hualei, Tang Zhaohui, Ren Xiang, Liu Mugen

机构信息

Key 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, China.

出版信息

Biomedicines. 2021 Nov 16;9(11):1699. doi: 10.3390/biomedicines9111699.

DOI:10.3390/biomedicines9111699
PMID:34829928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8616026/
Abstract

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 knockout () zebrafish model using CRISPR/Cas9 technology. The mutant inner ear displayed severe impairments, such as enlarged otocysts, smaller or absent otoliths, and insensitivity to sound stimulation. The proliferation of p63 epidermal stem cells and dlc ionocyte progenitors was inhibited in mutants. Moreover, the results showed that deletion induces the apoptosis of differentiated K-ATPase-rich (NR) cells and H-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.

摘要

斑马鱼是探索内耳发育的优秀模型。其内耳与人类内耳具有相似功能，尤其在听力和平衡的维持方面。Mafba是Maf转录因子家族的一个成员。它参与多种生物学过程，但其在内耳发育中的作用仍知之甚少。在本研究中，我们使用CRISPR/Cas9技术构建了一个Mafba基因敲除（）斑马鱼模型。Mafba突变体的内耳表现出严重缺陷，如耳囊扩大、耳石变小或缺失以及对声音刺激不敏感。在Mafba突变体中，p63表皮干细胞和dlc离子细胞祖细胞的增殖受到抑制。此外，结果表明，Mafba缺失诱导富含K-ATP酶（NR）的分化细胞和富含H-ATP酶（HR）的分化细胞凋亡。内耳区域的DNA损伤导致p53凋亡激活和G0/G1细胞周期停滞，这为内耳缺陷提供了一种解释机制。离子细胞祖细胞紊乱导致的内环境稳态丧失导致内耳结构缺陷，进而导致听力丧失。总之，本研究利用斑马鱼Mafba模型阐明了离子通道稳态在内耳发育中的功能，并阐明了其可能的生理作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/d7f74e32c36b/biomedicines-09-01699-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/f892c3aa268b/biomedicines-09-01699-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/ebd723e8c13c/biomedicines-09-01699-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/b64a54fb7d68/biomedicines-09-01699-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/a546a894cd95/biomedicines-09-01699-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/70ac6bf12ed3/biomedicines-09-01699-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/20de3d895a41/biomedicines-09-01699-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/126414843939/biomedicines-09-01699-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/d7f74e32c36b/biomedicines-09-01699-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/f892c3aa268b/biomedicines-09-01699-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/ebd723e8c13c/biomedicines-09-01699-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/b64a54fb7d68/biomedicines-09-01699-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/a546a894cd95/biomedicines-09-01699-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/70ac6bf12ed3/biomedicines-09-01699-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/20de3d895a41/biomedicines-09-01699-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/126414843939/biomedicines-09-01699-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d89/8616026/d7f74e32c36b/biomedicines-09-01699-g008.jpg

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