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Dicerl and miR-9 are required for proper Notchl signaling and the Bergmann glial phenotype in the developing mouse cerebellum

Dicerl and miR-9 are required for proper Notchl signaling an...

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中国神经科学学会第十届全国学术会议

作者： Yi KUANG Qian LIU Xiao-Qiong SHU Chi ZHANG Ning HUANG Jun LI Mei JIANG He-Dong LI West China Developmental c& Stem Cell Institute Sichuan University School of Life Science Sichuan University Department of Obstetric & Gynecologic and Pediatric Sichuan University Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects Ministry of Education West China Second University Hospital Sichuan University

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 ***,the functions of miRNAs during cerebellar development have not been systematically ***,we conditionally knocked out the Dicerl gene under the control of the human glial fibrillary acidic protein（hgfap） promoter to examine the effect of miRNAs in the developing *** particularly focused on the phenotype of Bergmann glia（BG）.The hgfap-Cre activity was detected as early as embryomc day 13.5（E13.5） at the rhombic lip（RL） in the cerebellar plate,and later in several postnatal cerebellar cell types,including *** ablation induces a smaller and less developed cerebellum,accompanied by aberrant BG *** signaling appears to be blocked in Dicerl-ablated BG,with reduced expression of the Notchl target gene,brain lipid binding protein（BLBP）.Using neuronal co-culture assays,we showed an intrinsic effect of Dicerl on BG morphology and Notchl target gene *** 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 Notchl signaling pathway in cultured BG cells.

关键词： hgfap Dicer Bergmann glia Notchl miR-9

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MicroRNA ablation affects Bergmann glial morphology and disrupts tissue morphogenesis in the developing mouse cerebellum

MicroRNA ablation affects Bergmann glial morphology and disr...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Q.Richard LU Department of Developmental Biology University of Texas Southwestern Medical CenterDallasTX 75390USA

＜正＞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 ***,miRNA functions during cerebellar development have not been systematically *** we conditionally knockout Dicer gene under the activity of human glial fibrillary acidic protein （hgfap） promoter to examine the effect of miRNAs in the developing *** 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 intemeurons and aberrant morphology of Bergmann *** addition,Notchl signaling appears to be blocked in miRNA-ablated Bergmann *** further identified miR-9 as differentially expressed in Bergmann glial cells,and its expression was promoted by Notchl *** 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 *** 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.

关键词： hgfap miR-9 Dicer Cre-flox Bergmann glia

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