Histone Demethylase PHF8 Is Required for the Development of the Zebrafish Inner Ear and Posterior Lateral Line.
Histone Demethylase PHF8 Is Required for the Development of the Zebrafish Inner Ear and Posterior Lateral Line.
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斑马鱼内耳和后侧线的发育需要组蛋白去甲基化酶 PHF8
DOI：
10.3389/fcell.2020.566504
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发表时间：
2020
影响因子：
5.5
通讯作者：
Cai C
中科院分区：
文献类型：
--
作者：
He J;Zheng Z;Luo X;Hong Y;Su W;Cai C
组蛋白去甲基化酶PHF8对多种发育过程至关重要，因此，需要提高对其在发育听觉器官中功能的认识。应用原位杂交技术（ISH）检测了斑马鱼侧线系统和耳泡中PHF 8 mRNA的表达。通过morpholino敲低PHF 8显著破坏了后侧线系统的发育，这影响了细胞迁移并减少了侧线神经瘤的数量。在内耳发育过程中，PHF 8的敲除还导致半规管和耳石在大小、数量和位置方面的严重畸形。PHF 8功能的丧失也诱导了侧线神经瘤和内耳中感觉毛细胞的分化缺陷。缺乏PHF8的胚胎的ISH分析显示，与细胞迁移和沉积有关的几种信号通路的许多靶基因的表达发生了变化，包括Wnt和FGF通路。总之，目前的研究结果确定PHF 8是听觉器官发育中的一种新的表观遗传因子，使其成为听力损失治疗的潜在候选者。
Histone demethylase PHF8 is crucial for multiple developmental processes, and hence, the awareness of its function in developing auditory organs needs to be increased. Using in situ hybridization (ISH) labeling, the mRNA expression of PHF8 in the zebrafish lateral line system and otic vesicle was monitored. The knockdown of PHF8 by morpholino significantly disrupted the development of the posterior lateral line system, which impacted cell migration and decreased the number of lateral line neuromasts. The knockdown of PHF8 also resulted in severe malformation of the semicircular canal and otoliths in terms of size, quantity, and position during the inner ear development. The loss of function of PHF8 also induced a defective differentiation in sensory hair cells in both lateral line neuromasts and the inner ear. ISH analysis of embryos that lacked PHF8 showed alterations in the expression of many target genes of several signaling pathways concerning cell migration and deposition, including the Wnt and FGF pathways. In summary, the current findings established PHF8 as a novel epigenetic element in developing auditory organs, rendering it a potential candidate for hearing loss therapy.