Article abstract
Nature Neuroscience 12, 399 - 408 (2009)
Published online: 15 March 2009 | doi:10.1038/nn.2294
miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche
Li-Chun Cheng1, Erika Pastrana1, Masoud Tavazoie2 & Fiona Doetsch1,2,3,4
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.
- Departments of Pathology and Cell Biology Columbia University, College of Physicians and Surgeons, New York, New York, USA.
- Department of Neuroscience, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
- Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
- Center for Motor Neuron Biology and Disease, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Correspondence to: Fiona Doetsch1,2,3,4 e-mail: fkd2101@columbia.edu
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