Journal
NATURE NEUROSCIENCE
Volume 14, Issue 9, Pages 1125-U177Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2897
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Funding
- Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST)
- Ministry of Education, Culture, Sports, Science and Technology
- Takeda Science Foundation
- Uehara Memorial Foundation
- Mochida Memorial Foundation
- Naito Foundation
- Grants-in-Aid for Scientific Research [22770071, 23592603, 23390074] Funding Source: KAKEN
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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.
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