miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche.
The subventricular zone (SVZ) is the largest neurogenic niche in the adult mammalian brain. We found that the brain-enriched microRNA miR-124 is an important regulator of the temporal progression of adult neurogenesis in mice. Knockdown of endogenous miR-124 maintained purified SVZ stem cells as dividing precursors, whereas ectopic expression led to precocious and increased neuron formation. Furthermore, blocking miR-124 function during regeneration led to hyperplasias, followed by a delayed burst of neurogenesis. We identified the SRY-box transcription factor Sox9 as being a physiological target of miR-124 at the transition from the transit amplifying cell to the neuroblast stage. Sox9 overexpression abolished neuronal differentiation, whereas Sox9 knockdown led to increased neuron formation. Thus miR-124-mediated repression of Sox9 is important for progression along the SVZ stem cell lineage to neurons.
Cheng
Li-Chun
LC
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Pastrana
Erika
E
Tavazoie
Masoud
M
Doetsch
Fiona
F
D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D001921:Brain; D001973:Bromodeoxyuridine / Q000378:metabolism; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D003561:Cytarabine / Q000494:pharmacology; D000089622:Doublecortin Domain Proteins; D004622:Embryo, Mammalian; D005434:Flow Cytometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D020547:Lateral Ventricles / Q000033:anatomy & histology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D055153:Stem Cell Niche / Q000166:cytology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods; D014404:Tubulin / Q000378:metabolism; D000099153:Pentraxins
D001973:Bromodeoxyuridine; D002097:C-Reactive Protein; D003561:Cytarabine; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D007166:Immunosuppressive Agents; D019394:Ki-67 Antigen; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D020319:Oligodeoxyribonucleotides, Antisense; D014157:Transcription Factors; D014404:Tubulin; D000099153:Pentraxins; C540079:Mirn124 microRNA, mouse; C462941:beta3 tubulin, mouse