Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Animals, Newborn
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Axons / physiology*
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Brain / abnormalities
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Cell Differentiation / genetics
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Cell Survival / genetics
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Electroporation / methods
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Electroretinography / methods
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Embryo, Mammalian
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Evoked Potentials, Visual / genetics
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Gene Expression Regulation, Developmental / genetics
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Hippocampus / cytology*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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In Situ Nick-End Labeling / methods
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LIM-Homeodomain Proteins
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Mice
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Mice, Transgenic
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Neurons / cytology*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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RNA, Untranslated / genetics
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Retina / cytology
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Retina / physiology
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Retinal Cone Photoreceptor Cells / physiology*
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Tissue Culture Techniques
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Transcription Factors / metabolism*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Homeodomain Proteins
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LIM-Homeodomain Proteins
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Lhx2 protein, mouse
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MicroRNAs
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Mirn124 microRNA, mouse
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RNA, Small Interfering
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RNA, Untranslated
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Transcription Factors
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Tumor Suppressor Proteins
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prospero-related homeobox 1 protein