title: Cerebellar granule cells are predominantly generated by terminal symmetric divisions of granule cell precursors.
abstract: BACKGROUND
  Neurons in the central nervous system (CNS) are generated by symmetric and asymmetric cell division of neural stem cells and their derivative progenitor cells. Cerebellar granule cells are the most abundant neurons in the CNS, and are generated by intensive cell division of granule cell precursors (GCPs) during postnatal development. Dysregulation of GCP cell cycle is causal for some subtypes of medulloblastoma. However, the details and mechanisms underlying neurogenesis from GCPs are not well understood.
  
  
  RESULTS
  Using long-term live-cell imaging of proliferating GCPs transfected with a fluorescent newborn-granule cell marker, we found that GCPs underwent predominantly symmetric divisions, generating two GCPs or two neurons, while asymmetric divisions generating a GCP and a neuron were only occasionally observed, in both dissociated culture and within tissues of isolated cerebellar lobules. We found no significant difference in cell cycle length between proliferative and neurogenic divisions, or any consistent changes in cell cycle length during repeated proliferative division.
  
  
  CONCLUSIONS
  Unlike neural stem cells in the cerebral cortex and spinal cord, which generate many neurons by repeated asymmetric division, cerebellar GCPs produce neurons predominantly by terminal symmetric division. These results indicate diverse mechanisms of neurogenesis in the mammalian brain.
authors.affiliation: Graduate School of Biostudies, Kyoto University, Yoshida Honmachi, Kyoto, Japan.
authors.forename: Kie
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Umeshima
authors.affiliation: Graduate School of Biostudies, Kyoto University, Yoshida Honmachi, Kyoto, Japan.|Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan.
authors.forename: Mineko
authors.initials: M
authors.lastname: Kengaku
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D015415:Biomarkers; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D017077:Culture Media, Conditioned; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics; D000089622:Doublecortin Domain Proteins; D005456:Fluorescent Dyes / Q000032:analysis; D017930:Genes, Reporter; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D059008:Time-Lapse Imaging
chemical_list: D015415:Biomarkers; C493961:Cdkn1b protein, mouse; D017077:Culture Media, Conditioned; D000089622:Doublecortin Domain Proteins; D005456:Fluorescent Dyes; D053823:Hedgehog Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C465570:Shh protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: cell cycle; live-cell imaging; medulloblastoma; neural stem cells; neurogenesis