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PMID: 19287386 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche.

Nature neuroscience ·Vol. 12 ·No. 4 ·2009-04-00 ·Pages 399-408

Cheng LC, Pastrana E, Tavazoie M, Doetsch F

Abstract

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.

MeSH Terms
Adult Stem Cells/physiology Animals Brain Bromodeoxyuridine/metabolism C-Reactive Protein/genetics,metabolism Cell Differentiation/drug effects,physiology Cells, Cultured Coculture Techniques/methods Cytarabine/pharmacology Doublecortin Domain Proteins Embryo, Mammalian Flow Cytometry/methods Glial Fibrillary Acidic Protein/metabolism Green Fluorescent Proteins/metabolism Immunosuppressive Agents/pharmacology Ki-67 Antigen/metabolism Lateral Ventricles/anatomy & histology Mice MicroRNAs/genetics,physiology Microtubule-Associated Proteins/metabolism Nerve Tissue Proteins/genetics,metabolism Neurogenesis/genetics,physiology Neuropeptides/metabolism Oligodeoxyribonucleotides, Antisense/pharmacology Stem Cell Niche/cytology Time Factors Transcription Factors/metabolism Transduction, Genetic/methods Tubulin/metabolism
Chemicals
Doublecortin Domain Proteins Glial Fibrillary Acidic Protein Immunosuppressive Agents Ki-67 Antigen MicroRNAs Microtubule-Associated Proteins Mirn124 microRNA, mouse Nerve Tissue Proteins Neuropeptides Oligodeoxyribonucleotides, Antisense Transcription Factors Tubulin beta3 tubulin, mouse neuronal pentraxin Cytarabine Green Fluorescent Proteins C-Reactive Protein Bromodeoxyuridine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cheng Li-Chun
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Pastrana Erika
Tavazoie Masoud
Doetsch Fiona
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.2294
Published
2009-04-00
Epub
2009-00-15
Pages
399-408
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC2766245
Subset
IM
Grants
NINDS NIH HHS · R01 NS053884 · United States
NIMH NIH HHS · T32 MH015174 · United States
NIMH NIH HHS · T32 MH015174-32 · United States
Corrections
CommentIn
PMID: 19322237
External Links
PubMed source DOI: 10.1038/nn.2294 PMC Full Text View journal details
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