miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression
miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression
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DOI：
10.1038/nn.2897
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发表时间：
2011-09-01
影响因子：
25
通讯作者：
Furukawa, Takahisa
中科院分区：
文献类型：
--
作者：
Sanuki, Rikako;Onishi, Akishi;Furukawa, Takahisa
microRNA-124 a（miR-124 a）是脊椎动物中枢神经系统中表达最丰富的microRNA。尽管过去对miR-124 a的作用进行了研究，但不一致的结果使miR-124 a的体内功能不清楚。我们通过靶向破坏Rncr 3（视网膜非编码RNA 3）（miR-124 a的主要来源）来检查miR-124 a的体内功能。Rncr 3（-/-）小鼠在CNS中表现出异常，包括小的脑尺寸、齿状回颗粒细胞的轴突错误发芽和视网膜锥细胞死亡。我们发现Lhx 2是miR-124 a的体内靶mRNA。我们还观察到，miR-124 a下调LHX 2是防止发育中的视网膜细胞凋亡和海马神经元轴突正常发育所必需的。这些结果表明，miR-124 a是至关重要的成熟和存活的齿状回神经元和视网膜锥，因为它抑制Lhx 2翻译。
MicroRNA-124a (miR-124a) is the most abundant microRNA expressed in the vertebrate CNS. Despite past investigations into the role of miR-124a, inconsistent results have left the in vivo function of miR-124a unclear. We examined the in vivo function of miR-124a by targeted disruption of Rncr3 (retinal non-coding RNA 3), the dominant source of miR-124a. Rncr3(-/-) mice exhibited abnormalities in the CNS, including small brain size, axonal mis-sprouting of dentate gyrus granule cells and retinal cone cell death. We found that Lhx2 is an in vivo target mRNA of miR-124a. We also observed that LHX2 downregulation by miR-124a is required for the prevention of apoptosis in the developing retina and proper axonal development of hippocampal neurons. These results suggest that miR-124a is essential for the maturation and survival of dentate gyrus neurons and retinal cones, as it represses Lhx2 translation.