title: Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.
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.
  
  
  RESULTS
  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 enriched in nonneuronal genes, which is consistent with previous studies in vitro. Microarray data mining showed that upregulated genes were enriched in biological processes related to gene expression regulation, while downregulated genes were associated with neuronal functions. Molecular pathways associated with neurological disorders, cellular organization and cellular maintenance were altered in the Dicer mutant mice. Numerous miRNA target sites were enriched in the 3'untranslated region (3'UTR) of upregulated genes, the most significant corresponding to the miR-124 seed sequence. Interestingly, our results suggest that, in addition to miR-124, a large fraction of the neuronal miRNome participates, by order of abundance, in coordinated gene expression regulation and neuronal maintenance.
  
  
  CONCLUSIONS
  Taken together, these results provide new clues into the role of specific miRNA pathways in the regulation of brain identity and maintenance in adult mice.
authors.affiliation: Axe Neurosciences, Centre de Recherche du CHUQ (CHUL), Québec, Québec, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dorval
authors.forename: Pascal Y
authors.initials: PY
authors.lastname: Smith
authors.forename: Charlotte
authors.initials: C
authors.lastname: Delay
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Calvo
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Planel
authors.forename: Nadège
authors.initials: N
authors.lastname: Zommer
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: Sébastien S
authors.initials: SS
authors.lastname: Hébert
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D019295:Computational Biology; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D015203:Reproducibility of Results; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases