Dicer1 and MiR-9 are required for proper Notch1 signaling and the Bergmann glial phenotype in the developing mouse cerebellum
Dicer1 and MiR-9 are required for proper Notch1 signaling and the Bergmann glial phenotype in the developing mouse cerebellum
复制标题
Dicer1 和 MiR-9 对于发育中的小鼠小脑中正确的 Notch1 信号传导和 Bergmann 神经胶质表型是必需的
DOI：
10.1002/glia.22392
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发表时间：
2012-11-01
期刊：
影响因子：
6.2
通讯作者：
Li, Hedong
中科院分区：
文献类型：
--
作者：
Kuang, Yi;Liu, Qian;Li, Hedong
MicroRNAs （miRNAs）在中枢神经系统（CNS）的发育中起着重要的作用。一些报道表明，在没有mirna的情况下，发育中的前脑的组织发育和细胞分化被破坏。然而，在小脑发育过程中，mirna的功能尚未被系统地表征。在这里，我们在人类胶质纤维酸性蛋白（hGFAP）启动子的控制下，有条件地敲除Dicer1基因，以研究mirna在发育中的小脑中的作用。我们特别关注伯格曼胶质细胞（BG）的表型。早在胚胎第13.5天（E13.5），在小脑板的菱形唇（RL）就检测到hgmap - cre的活性，随后在出生后的几种小脑细胞类型（包括BG）中检测到。Dicer1消融导致小脑变小，发育不全，并伴有异常的BG形态。在dicer1消融的BG中，Notch1信号通路似乎被阻断，Notch1靶基因脑脂结合蛋白（BLBP）的表达减少。通过神经元共培养实验，我们发现Dicer1对BG形态和Notch1靶基因表达的内在影响。我们进一步确定了miR-9在BG中的差异表达，并表明miR-9是培养BG细胞中Notch1信号通路的关键miRNA组分，但不是唯一的miRNA组分。(c) 2012 Wiley期刊有限公司
MicroRNAs (miRNAs) have important roles in the development of the central nervous system (CNS). Several reports indicate that tissue development and cellular differentiation in the developing forebrain are disrupted in the absence of miRNAs. However, the functions of miRNAs during cerebellar development have not been systematically characterized. Here, we conditionally knocked out the Dicer1 gene under the control of the human glial fibrillary acidic protein (hGFAP) promoter to examine the effect of miRNAs in the developing cerebellum. We particularly focused on the phenotype of Bergmann glia (BG). The hGFAP-Cre activity was detected as early as embryonic day 13.5 (E13.5) at the rhombic lip (RL) in the cerebellar plate, and later in several postnatal cerebellar cell types, including BG. Dicer1 ablation induces a smaller and less developed cerebellum, accompanied by aberrant BG morphology. Notch1 signaling appears to be blocked in Dicer1-ablated BG, with reduced expression of the Notch1 target gene, brain lipid binding protein (BLBP). Using neuronal co-culture assays, we showed an intrinsic effect of Dicer1 on BG morphology and Notch1 target gene expression. We further identified miR-9 as being differentially expressed in BG and showed that miR-9 is a critical, but not the only, miRNA component of the Notch1 signaling pathway in cultured BG cells. (c) 2012 Wiley Periodicals, Inc.