MicroRNA ablation affects Bergmann glial morphology and disrupts tissue morphogenesis in the develop

来源 :中国神经科学学会第九届全国学术会议暨第五届会员代表大会 | 被引量 : 0次 | 上传用户:shen648491077
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  MicroRNAs (miRNAs) play important roles during development of the central nervous system (CNS).Several reports indicate that tissue development and cellular differentiation in the developing forebrains are disrupted in the absence of miRNAs.However, miRNA functions during cerebellar development have not been systematically characterized.Here we conditionally knockout Dicer gene under the activity of human glial fibrillary acidic protein (hGFAP) promoter to examine the effect ofmiRNAs in the developing cerebellum.We found that ablation of miRNAs resulted in a smaller cerebellum, mis-positioned Purkinje neurons, decreased proliferation and increased apoptosis in granule neuron precursors, decreased number of basket and stellate interneurons and aberrant morphology of Bergmann glia.In addition, Noteh 1 signaling appears to be blocked in miRNA-ablated Bergmann glia.We further identified miR-9 as differentially expressed in Bergmann glial cells, and its expression was promoted by Notch 1activation.We also demonstrated that cortical radial glia exhibited normal morphology in the absence of miRNAs and yet reduced radial glial marker expression at embryonic stage, and that the postnatal radial glial transition to astrocytes was promoted in miRNA-ablated forebrains.These results further stressed the critical involvement of miRNAs in the developing CNS including cerebellum and provided first evidence of differential miRNA function in regulating radial glial phenotype in different regions of the developing CNS.
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