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Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain

机译:miR-19在成人脑中新生神经元迁移中的功能意义

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Altered microRNA profiles have been implicated in human brain disorders. However, the functional contribution of individual microRNAs to neuronal development and function is largely unknown. Here, we report biological functions for miR-19 in adult neurogenesis. We determined that miR-19 is enriched in neural progenitor cells (NPCs) and downregulated during neuronal development in the adult hippocampus. By manipulating miR-19 in NPCs for gain-and loss-of-function studies, we discovered that miR-19 regulates cell migration by directly targeting Rapgef2. Concordantly, dysregulation of miR-19 in NPCs alters the positioning of newborn neurons in the adult brain. Furthermore, we found abnormal expression of miR-19 in human NPCs generated from schizophrenic patient-derived induced pluripotent stem cells (iPSCs) that have been described as displaying aberrant migration. Our study demonstrates the significance of posttranscriptional gene regulation by miR-19 in preventing the irregular migration of adult-born neurons that may contribute to the etiology of schizophrenia.
机译:改变的microRNA谱图与人类脑部疾病有关。但是,单个microRNA对神经元发育和功能的功能贡献在很大程度上是未知的。在这里,我们报告miR-19在成人神经发生中的生物学功能。我们确定miR-19在成人海马神经元发育过程中富含神经祖细胞(NPC)并下调。通过操纵NPC中的miR-19进行功能获得和功能丧失研究,我们发现miR-19通过直接靶向Rapgef2来调节细胞迁移。相应地,NPC中miR-19的失调会改变新生神经元在成人大脑中的位置。此外,我们发现在精神分裂症患者衍生的诱导多能干细胞(iPSC)生成的人NPC中,miR-19的异常表达已被描述为显示出异常的迁移。我们的研究证明了miR-19调节转录后基因在预防成年出生的神经元的不规则迁移中的重要性,该异常迁移可能有助于精神分裂症的病因。

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