title: Loss of functional Dicer in mouse radial glia cell-autonomously prolongs cortical neurogenesis.
abstract: Radial glia of the mouse cerebral cortex emerge from neuroepithelial stem cells around embryonic day 11 and produce excitatory cortical neurons until a few days before birth. The molecular mechanisms that regulate the end of cortical neurogenesis remain largely unknown. Here we investigated if the Dicer-dependent microRNA (miRNA) pathway is involved. By electroporating a cre-recombinase expression vector into the cortex of E13.5 embryos carrying a conditional allele of Dicer1, we induced mosaic recombination causing Dicer1 deletion and reporter activation in a subset of radial glia. We analysed the long-term fates of their progeny. We found that mutant radial glia produced abnormally large numbers of Cux1-positive neurons, many of which populated the superficial cortical layers. Injections of the S-phase marker bromodeoxyuridine between postnatal days 3 and 14 showed that much of this population was generated postnatally. Our findings suggest a role for Dicer-dependent processes in limiting the timespan of cortical neurogenesis.
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK. Electronic address: tomasz.j.nowakowski@gmail.com.
authors.forename: Tomasz Jan
authors.initials: TJ
authors.lastname: Nowakowski
authors.forename: Karolina Sandra
authors.initials: KS
authors.lastname: Mysiak
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Leary
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Fotaki
authors.forename: Thomas
authors.initials: T
authors.lastname: Pratt
authors.forename: David Jonathan
authors.initials: DJ
authors.lastname: Price
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D004622:Embryo, Mammalian / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Dicer; Mouse; Neurogenesis; Telencephalon; microRNA