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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Kruppel-like factor 9 is necessary for late-phase neuronal maturation in the developing dentate gyrus and during adult hippocampal neurogenesis.
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Kruppel-like factor 9 is necessary for late-phase neuronal maturation in the developing dentate gyrus and during adult hippocampal neurogenesis.

机译：Kruppel样因子9对于发育中的齿状回和成年海马神经发生后期神经元成熟是必需的。

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摘要

The dentate gyrus (DG) is modified throughout life by integration of new adult-born neurons. Similarities in neuronal maturation during DG development and adult hippocampal neurogenesis suggest that genetically encoded intrinsic regulatory mechanisms underlying these temporally distinct processes are conserved and reused. Here, we identify a novel transcriptional regulator of dentate granule neuron maturation, Kruppel-like factor 9 (Klf-9). We show that Klf-9 expression is induced by neuronal activity and as dentate granule neurons functionally integrate in the developing and adult DG. During development, dentate granule neurons lacking Klf-9 show delayed maturation as reflected by altered expression of early-phase markers, dendritic spine formation, and electrophysiological properties. Adult Klf-9-null mice exhibit normal stem cell proliferation and cell fate specification in the DG but show impaired differentiation of adult-born neurons and decreased neurogenesis-dependent synaptic plasticity. Behavioral analysis of Klf-9-null mice revealed a subtle increase in anxiety-like behavior and an impairment in contextual fear discrimination learning. Thus, Klf-9 is necessary for late-phase maturation of dentate granule neurons both in DG development and during adult hippocampal neurogenesis. Klf-9-dependent neuronal maturation may therefore represent a candidate regulatory mechanism underlying these temporally distinct processes.
机译：齿状回（DG）通过整合成年新生的神经元在整个生命中得到修饰。 DG发育和成年海马神经发生过程中神经元成熟的相似性表明，保留并重复使用了遗传编码的内在调节机制，这些机制是这些暂时不同的过程的基础。在这里，我们确定了齿状颗粒神经元成熟，Kruppel样因子9（Klf-9）的新型转录调控因子。我们显示，Klf-9表达是由神经元活性诱导的，并且作为齿状颗粒神经元功能性整合在发育中的和成年的DG中。在发育过程中，缺乏Klf-9的齿状颗粒神经元显示出成熟的延迟，这反映在早期标志物表达的改变，树突状脊柱的形成和电生理特性上。成年Klf-9无效小鼠在DG中显示正常的干细胞增殖和细胞命运特征，但显示成年出生的神经元分化受损，并且神经发生依赖性突触可塑性降低。对Klf-9无效小鼠的行为分析显示，焦虑样行为略有增加，而上下文恐惧歧视学习受到损害。因此，Klf-9对于DG发育和成年海马神经发生过程中齿状颗粒神经元的后期成熟是必需的。因此，依赖Klf-9的神经元成熟可能代表了这些时间上不同的过程的潜在调控机制。

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