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Nat Neurosci. 2011 Aug 21;14(9):1125-34. doi: 10.1038/nn.2897.

miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression.

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1
Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka, Japan.

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.

PMID:
21857657
DOI:
10.1038/nn.2897
[Indexed for MEDLINE]
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