Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, 300071, China.
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.
Cell Death Dis. 2018 Feb 15;9(3):273. doi: 10.1038/s41419-018-0337-z.
Interleukin 7 receptor (il7r), a transmembrane receptor, belongs to the type I cytokine receptor family. Il7r is involved in the pathogenesis of neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown of il7r leads to delayed myelination, highlighting the potential role of il7r in the development of the nervous system. Zebrafish is an ideal model for the study of neurogenesis; moreover, the il7r gene is highly conserved between zebrafish and human. The aim of the present study was to investigate the novel function of il7r in neurogenesis. First, an il7r homozygous mutant line was generated by clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. Second, the gross development of il7r mutants revealed remarkably smaller eyes and delayed retinal neurodifferentiation. Third, microarray analysis revealed that genes associated with the phototransduction signalling pathway were strongly down-regulated in il7r mutants. Finally, the results from behavioural tests indicated that visual function was impaired in il7r mutant larvae. Overall, our data demonstrate that a lack of il7r retards the development of the retina. Thus, il7r is an essential molecule for maintaining normal retinal development in zebrafish.
白细胞介素 7 受体(il7r)是一种跨膜受体,属于 I 型细胞因子受体家族。il7r 参与神经退行性疾病的发病机制,如多发性硬化症。il7r 的靶向敲低导致髓鞘形成延迟,突出了 il7r 在神经系统发育中的潜在作用。斑马鱼是研究神经发生的理想模型;此外,il7r 基因在斑马鱼和人类之间高度保守。本研究旨在探讨 il7r 在神经发生中的新功能。首先,通过成簇规律间隔短回文重复序列(CRISPR)相关 9 (CRISPR/Cas9)技术生成了 il7r 纯合突变系。其次,il7r 突变体的大体发育显示眼睛明显变小,视网膜神经分化延迟。第三,微阵列分析显示,il7r 突变体中与光转导信号通路相关的基因强烈下调。最后,行为测试的结果表明,il7r 突变体幼虫的视觉功能受损。总之,我们的数据表明,缺乏 il7r 会延迟视网膜的发育。因此,il7r 是维持斑马鱼正常视网膜发育所必需的分子。