Timing specific requirement of microRNA function is essential for embryonic and postnatal hippocampal development.

Timing specific requirement of microRNA function is essential for embryonic and postnatal hippocampal development.
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DOI:
10.1371/journal.pone.0026000
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Sun T
Sun T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li Q;Bian S;Hong J;Kawase-Koga Y;Zhu E;Zheng Y;Yang L;Sun T

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成年海马由齿状回(DG)和CA1、CA2和CA3区域组成,并且对于学习和记忆功能是必需的。在胚胎发育过程中,海马神经元来源于海马神经上皮细胞和齿状颗粒祖细胞。控制海马祖细胞增殖和分化的分子机制还不清楚。在这里,我们表明,非编码microRNAs(miRNAs)是必不可少的早期海马发育小鼠。在不同的胚胎时间点使用三个Cre小鼠系连续切除RNA酶III酶Dicer导致异常海马形态,并由于改变的增殖和增加的凋亡而影响海马祖细胞的数量。在早期阶段缺乏miRNA导致海马神经元的早期分化,特别是在CA1和DG区域。在后期阶段缺乏miRNAs特异性地影响CA3区域中的神经元产生。我们的研究结果揭示了特定海马区域形成的miRNAs的时间要求,其中CA1和DG的发育受到早期miRNAs丢失和CA3区域到晚期miRNAs丢失的阻碍。总的来说,我们的研究表明Dicer介导的miRNA通路在海马发育和功能中的重要性。
The adult hippocampus consists of the dentate gyrus (DG) and the CA1, CA2 and CA3 regions and is essential for learning and memory functions. During embryonic development, hippocampal neurons are derived from hippocampal neuroepithelial cells and dentate granular progenitors. The molecular mechanisms that control hippocampal progenitor proliferation and differentiation are not well understood. Here we show that noncoding microRNAs (miRNAs) are essential for early hippocampal development in mice. Conditionally ablating the RNAase III enzyme Dicer at different embryonic time points utilizing three Cre mouse lines causes abnormal hippocampal morphology and affects the number of hippocampal progenitors due to altered proliferation and increased apoptosis. Lack of miRNAs at earlier stages causes early differentiation of hippocampal neurons, in particular in the CA1 and DG regions. Lack of miRNAs at a later stage specifically affects neuronal production in the CA3 region. Our results reveal a timing requirement of miRNAs for the formation of specific hippocampal regions, with the CA1 and DG developmentally hindered by an early loss of miRNAs and the CA3 region to a late loss of miRNAs. Collectively, our studies indicate the importance of the Dicer-mediated miRNA pathway in hippocampal development and functions.
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