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

机译:miR-124调节脑室下干细胞生态位中的成年神经发生。

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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.
机译:室下区(SVZ)是成年哺乳动物脑中最大的神经源利基。我们发现,富含大脑的microRNA miR-124是小鼠成年神经发生的时间进程的重要调节剂。击倒内源性miR-124维持纯化的SVZ干细胞为分裂前体,而异位表达导致早熟和增加的神经元形成。此外,在再生过程中阻断miR-124功能会导致增生,随后是神经发生的延迟爆发。我们确定SRY框转录因子Sox9是miR-124在从转运扩增细胞到成神经细胞阶段的过渡过程中的生理目标。 Sox9的过表达消除了神经元分化,而Sox9的敲低导致神经元形成增加。因此,miR-124介导的Sox9抑制对于沿着SVZ干细胞谱系发展为神经元至关重要。

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