Knockout of <i>dhx38</i> Causes Inner Ear Developmental Defects in Zebrafish

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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
Subjects:
inner ear development
<i>dhx38</i>
zebrafish
cell apoptosis
DNA damage
Online Access:https://www.mdpi.com/2227-9059/13/1/20
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Summary:<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.
ISSN:2227-9059

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