microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus
microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus
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DOI：
10.1073/pnas.1015691107
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发表时间：
2010-11-23
影响因子：
11.1
通讯作者：
Goodman, Richard H.
中科院分区：
文献类型：
--
作者：
Magill, Stephen T.;Cambronne, Xiaolu A.;Goodman, Richard H.
成年海马齿状回新生神经元依赖cAMP反应元件结合蛋白（CREB）信号向成熟颗粒细胞分化并融入齿状网络。在其众多靶标中，转录因子CREB激活一个基因位点的表达，该基因位点产生两种microrna， miR-132和miR-212。在培养的皮质和海马神经元中，miR-132在CREB下游发挥作用，根据多种信号通路介导活动依赖性树突生长和脊柱形成。为了研究miR-132和/或miR-212是否有助于成年海马新生神经元树突的成熟，我们在miR-212/132位点周围插入LoxP位点，并通过立体定向注射表达Cre重组酶的逆转录病毒特异性靶向其缺失。miR212/132位点的缺失导致树突长度、乔木化和脊柱密度的急剧减少。miR-212/132位点可以表达多达四种不同的microrna， miR-132和-212及其反向链miR-132*和-212*。使用比例microRNA传感器，我们确定miR-132是海马神经元中的主要活性产物。我们得出结论，miR-132是成年海马新生神经元正常树突成熟所必需的，并表明该microRNA也可能参与creb介导的其他信号传导。
Newborn neurons in the dentate gyrus of the adult hippocampus rely upon cAMP response element binding protein (CREB) signaling for their differentiation into mature granule cells and their integration into the dentate network. Among its many targets, the transcription factor CREB activates expression of a gene locus that produces two microRNAs, miR-132 and miR-212. In cultured cortical and hippocampal neurons, miR-132 functions downstream from CREB to mediate activity-dependent dendritic growth and spine formation in response to a variety of signaling pathways. To investigate whether miR-132 and/or miR-212 contribute to the maturation of dendrites in newborn neurons in the adult hippocampus, we inserted LoxP sites surrounding the miR-212/132 locus and specifically targeted its deletion by stereotactically injecting a retrovirus expressing Cre recombinase. Deletion of the miR212/132 locus caused a dramatic decrease in dendrite length, arborization, and spine density. The miR-212/132 locus may express up to four distinct microRNAs, miR-132 and -212 and their reverse strands miR-132* and -212*. Using ratiometric microRNA sensors, we determined that miR-132 is the predominantly active product in hippocampal neurons. We conclude that miR-132 is required for normal dendrite maturation in newborn neurons in the adult hippocampus and suggest that this microRNA also may participate in other examples of CREB-mediated signaling.