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

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Abstract
This study shows that the microRNA miR-124 is required for neuronal differentiation of adult neural progenitors in vitro and in vivo. The transcription factor Sox9 opposes neuronal differentiation and is suppressed by miRNA-124. 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.