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


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.

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  1. Departments of Pathology and Cell Biology Columbia University, College of Physicians and Surgeons, New York, New York, USA.
  2. Department of Neuroscience, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
  3. Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
  4. 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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