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


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.

SUBMITTER: Cheng LC 

PROVIDER: S-EPMC2766245 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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

Cheng Li-Chun LC   Pastrana Erika E   Tavazoie Masoud M   Doetsch Fiona F  

Nature neuroscience 20090315 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 bur  ...[more]

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