title: Dicer is required for neural stem cell multipotency and lineage progression during cerebral cortex development.
abstract: BACKGROUND
  During cerebral cortex development, multipotent neural progenitor cells generate a variety of neuronal subtypes in a fixed temporal order. How a single neural progenitor cell generates the diversity of cortical projection neurons in a temporal sequence is not well understood. Based on their function in developmental timing in other systems, Dicer and microRNAs are potential candidate regulators of cellular pathways that control lineage progression in neural systems.
  
  
  RESULTS
  Cortex-specific deletion of Dicer results in a marked reduction in the cellular complexity of the cortex, due to a pronounced narrowing in the range of neuronal types generated by Dicer-null cortical stem and progenitor cells. Instead of generating different classes of lamina-specific neurons in order over the 6-day period of neurogenesis, Dicer null cortical stem and progenitor cells continually produce one class of deep layer projection neuron. However, gliogenesis in the Dicer-null cerebral cortex was not delayed, despite the loss of multipotency and the failure of neuronal lineage progression.
  
  
  CONCLUSIONS
  We conclude that Dicer is required for regulating cortical stem cell multipotency with respect to neuronal diversity, without affecting the larger scale switch from neurogenesis to gliogenesis. The differences in phenotypes reported from different timings of Dicer deletion indicate that the molecular pathways regulating developmental transitions are notably dosage sensitive.
authors.affiliation: Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Saurat
authors.forename: Therese
authors.initials: T
authors.lastname: Andersson
authors.forename: Navneet A
authors.initials: NA
authors.lastname: Vasistha
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Molnár
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Livesey
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
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