PDF(Pubmed)
Abstract：
CHD7, an encoding ATP-dependent chromodomain helicase DNA-binding protein 7, has been identified as the causative gene involved in CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia choanae, Retardation of growth and/or development, Genital abnormalities and Ear abnormalities). Although studies in rodent models have expanded our understanding of CHD7, its role in oligodendrocyte (OL) differentiation and myelination in zebrafish is still unclear. In this study, we generated a chd7-knockout strain with CRISPR/Cas9 in zebrafish. We observed that knockout (KO) of chd7 intensely impeded the oligodendrocyte progenitor cells\' (OPCs) migration and myelin formation due to massive expression of chd7 in oilg2+ cells, which might provoke upregulation of the MAPK signal pathway. Thus, our study demonstrates that chd7 is critical to oligodendrocyte migration and myelination during early development in zebrafish and describes a mechanism potentially associated with CHARGE syndrome.
摘要：
CHD7是一种编码ATP依赖性色域解旋酶DNA结合蛋白7的基因，已被鉴定为与CHARGE综合征有关的致病基因（眼睛的Coloboma，心脏缺陷,钩虫,生长和/或发育迟缓，生殖器异常和耳朵异常）。尽管啮齿动物模型的研究扩大了我们对CHD7的理解，但其在斑马鱼少突胶质细胞（OL）分化和髓鞘形成中的作用仍不清楚。在这项研究中,我们在斑马鱼中使用CRISPR/Cas9产生了chd7基因敲除菌株。我们观察到，由于chd7在oilg2+细胞中的大量表达，chd7的敲除（KO）强烈阻碍少突胶质祖细胞（OPCs）迁移和髓鞘形成，这可能会引起MAPK信号通路的上调。因此，我们的研究表明,chd7对斑马鱼早期发育过程中少突胶质细胞迁移和髓鞘形成至关重要,并描述了一种可能与CHARGE综合征相关的机制.
