gene network and pathway analysis of mice with conditional ablation of dicer in post-mitotic neurons基因网络和通路分析小鼠条件消融post-mitotic神经元的帽子.pdfVIP

Gene Network and Pathway Analysis of Mice with Conditional Ablation of Dicer in Post-Mitotic Neurons ´ 1,2 1,2 1,2 1,2 1,2 Veronique Dorval , Pascal Y. Smith , Charlotte Delay , Ezequiel Calvo , Emmanuel Planel , ` 3,4 ´ 3,4 ´ ´ 1,2 Nadege Zommer , Luc Buee , Sebastien S. Hebert * ´ ´ ´ ´ ´ 1 Axe Neurosciences, Centre de Recherche du CHUQ (CHUL), Quebec, Quebec, Canada, 2 Departement de Psychiatrie et de Neurosciences, Universite Laval, Quebec, ´ ´ ´ ´ Quebec, Canada, 3 Universite Lille-Nord de France, UDSL, Faculte de Medecine, Lille, France, 4 Inserm, UMR837, Lille, France Abstract Background: The small non-protein-coding microRNAs (miRNAs) have emerged as critical regulators of neuronal differentiation, identity and survival. To date, however, little is known about the genes and molecular networks regulated by neuronal miRNAs in vivo, particularly in the adult mammalian brain. Methodology/Principal Findings: We analyzed whole genome microarrays from mice lacking Dicer, the enzyme responsible for miRNA production, specifically in postnatal forebrain neurons. A total of 755 mRNA transcripts were significantly (P,0.05, FDR,0.25) misregulated in the conditional Dicer knockout mice. Ten genes, including Tnrc6c, Dnmt3a, and Limk1, were validated by real time quantitative RT-PCR. Upregulated transcripts were e