title: MiR-30e and miR-181d control radial glia cell proliferation via HtrA1 modulation.
abstract: The precise mechanisms by which microRNAs (miRNAs) contribute to the dynamic regulation of gene expression during the forebrain development are still partly elusive. Here we show that the depletion of miRNAs in the cerebral cortex and hippocampus, via genetic inactivation of Dicer after the onset of forebrain neurogenesis, profoundly impairs the morphological and proliferative characteristics of neural stem and progenitor cells. The cytoarchitecture and self-renewal potential of radial glial (RG) cells located within the cerebral cortex and the hippocampus were profoundly altered, thus causing a significant derangement of both the post natal dorsal sub-ventricular zone and the dentate gyrus. This effect was attributed to the High-temperature requirement A serine peptidase 1 (HtrA1) gene product whose overexpression in the developing forebrain recapitulated some of the aspects of the Dicer(-/-) phenotype. MiR-30e and miR-181d were identified as posttranscriptional negative regulators of HtrA1 by binding to its 3' untranslated region. In vivo overexpression of miR-30e and miR-181d in Dicer(-/-) forebrain rescued RG proliferation defects.
authors.affiliation: Neuroimmunology Unit, INSpe, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Nigro
authors.forename: R
authors.initials: R
authors.lastname: Menon
authors.forename: A
authors.initials: A
authors.lastname: Bergamaschi
authors.forename: Y M
authors.initials: YM
authors.lastname: Clovis
authors.forename: A
authors.initials: A
authors.lastname: Baldi
authors.forename: M
authors.initials: M
authors.lastname: Ehrmann
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: D
authors.initials: D
authors.lastname: De Pietri Tonelli
authors.forename: C
authors.initials: C
authors.lastname: Farina
authors.forename: G
authors.initials: G
authors.lastname: Martino
authors.forename: L
authors.initials: L
authors.lastname: Muzio
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein; D057809:HEK293 Cells; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D016548:Prosencephalon / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D005904:Glial Fibrillary Acidic Protein; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse; C529100:mirn181 microRNA, mouse; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D000074289:High-Temperature Requirement A Serine Peptidase 1; C492073:HtrA1 protein, mouse; D012697:Serine Endopeptidases; D053487:DEAD-box RNA Helicases