miRNAs are Essential for the Survival and Maturation of Cortical Interneurons.
miRNAs are Essential for the Survival and Maturation of Cortical Interneurons.
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DOI：
10.1093/cercor/bht426
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发表时间：
2015-07
期刊：
影响因子：
3.7
通讯作者：
Sebnem N. Tuncdemir;G. Fishell;R. Batista-Brito
中科院分区：
文献类型：
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作者：
Sebnem N. Tuncdemir;G. Fishell;R. Batista-Brito
复杂而精确的遗传程序有助于皮质gaba能中间神经元（cIN）的产生、迁移和成熟。然而，介导基因表达快速改变的信号却知之甚少，而基因表达的快速改变是cINs在皮层中经过一系列发育步骤导致其成熟特性所必需的。在这里，我们研究了microrna转录后调控基因表达对cIN前体发育的作用。我们发现有条件地去除RNAseIII酶Dicer可减少成年小鼠中cINs的数量。Dicer对cINs的形态和分子成熟也是必需的。成熟mirna的缺失通过损害cINs细胞类型的迁移和分化来影响cINs的发育，同时保持祖细胞的增殖不受干扰。这些发育缺陷与参与细胞凋亡和神经元分化的分子的异常表达密切相关。此外，我们还发现了几个在有丝分裂后cINs中选择性上调的mirna，这与mirna在cINs成熟所必需的分化和凋亡程序的转录后控制中的作用一致。因此，我们的研究结果表明，cIN祖细胞需要dicer依赖机制来微调cINs的迁移和成熟。
Complex and precisely orchestrated genetic programs contribute to the generation, migration, and maturation of cortical GABAergic interneurons (cIN). Yet, little is known about the signals that mediate the rapid alterations in gene expression that are required for cINs to transit through a series of developmental steps leading to their mature properties in the cortex. Here, we investigated the function of post-transcriptional regulation of gene expression by microRNAs on the development of cIN precursors. We find that conditional removal of the RNAseIII enzyme Dicer reduces the number of cINs in the adult mouse. Dicer is further necessary for the morphological and molecular maturation of cINs. Loss of mature miRNAs affects cINs development by impairing migration and differentiation of this cell type, while leaving proliferation of progenitors unperturbed. These developmental defects closely matched the abnormal expression of molecules involved in apoptosis and neuronal specification. In addition, we identified several miRNAs that are selectively upregulated in the postmitotic cINs, consistent with a role of miRNAs in the post-transcriptional control of the differentiation and apoptotic programs essential for cIN maturation. Thus, our results indicate that cIN progenitors require Dicer-dependent mechanisms to fine-tune the migration and maturation of cINs.