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首页> 外文期刊>G3: Genes, Genomes, Genetics >Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish
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Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish

机译：纤毛相关基因在斑马鱼中氨基糖苷诱导的毛细胞死亡中起着不同的作用

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摘要

Hair cells possess a single primary cilium, called the kinocilium, early in development. While the kinocilium is lost in auditory hair cells of most species it is maintained in vestibular hair cells. It has generally been believed that the primary role of the kinocilium and cilia-associated genes in hair cells is in the establishment of the polarity of actin-based stereocilia, the hair cell mechanotransduction apparatus. Through genetic screening and testing of candidate genes in zebrafish (Danio rerio) we have found that mutations in multiple cilia genes implicated in intraflagellar transport ( dync2h1 , wdr35 , ift88 , and traf3ip) , and the ciliary transition zone ( cc2d2a , mks1 , and cep290 ) lead to resistance to aminoglycoside-induced hair cell death. These genes appear to have differing roles in hair cells, as mutations in intraflagellar transport genes, but not transition zone genes, lead to defects in kinocilia formation and processes dependent upon hair cell mechanotransduction activity. These mutants highlight a novel role of cilia-associated genes in hair cells, and provide powerful tools for further study.
机译：毛细胞在发育的早期具有单个初级纤毛，称为运动毛囊。在大多数物种的听觉毛细胞中失去了运动蛋白，而在前庭毛细胞中却保留了。人们普遍认为，毛细胞中毛囊动蛋白和纤毛相关基因的主要作用是建立基于肌动蛋白的立体纤毛的极性，即毛细胞机械转导装置。通过遗传筛选和测试斑马鱼（Danio rerio）中的候选基因，我们发现多个纤毛基因的突变与鞭毛内运输有关（dync2h1，wdr35，ift88和traf3ip），以及睫状过渡区（cc2d2a，mks1和cep290） ）导致对氨基糖苷诱导的毛细胞死亡的抵抗。这些基因似乎在毛细胞中具有不同的作用，因为鞭毛内转运基因的突变而非过渡区基因的突变会导致毛发生在巨噬细胞的形成和取决于毛细胞机械转导活性的过程中。这些突变体突出了纤毛相关基因在毛细胞中的新作用，并为进一步研究提供了有力工具。

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