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

Rikako Sanuki; Akishi Onishi; Chieko Koike; Rieko Muramatsu; Satoshi Watanabe; Yuki Muranishi; Shoichi Irie; Shinji Uneo; Toshiyuki Koyasu; Ryosuke Matsui; Yoan Chérasse; Yoshihiro Urade; Dai Watanabe; Mineo Kondo; Toshihide Yamashita; Takahisa Furukawa

doi:10.1038/nn.2897

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

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

Authors

Rikako Sanuki¹, Akishi Onishi, Chieko Koike, Rieko Muramatsu, Satoshi Watanabe, Yuki Muranishi, Shoichi Irie, Shinji Uneo, Toshiyuki Koyasu, Ryosuke Matsui, Yoan Chérasse, Yoshihiro Urade, Dai Watanabe, Mineo Kondo, Toshihide Yamashita, Takahisa Furukawa

Affiliation

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

PMID: 21857657
DOI: 10.1038/nn.2897

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

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Animals, Newborn
Axons / physiology*
Brain / abnormalities
Cell Differentiation / genetics
Cell Survival / genetics
Electroporation / methods
Electroretinography / methods
Embryo, Mammalian
Evoked Potentials, Visual / genetics
Gene Expression Regulation, Developmental / genetics
Hippocampus / cytology*
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
In Situ Nick-End Labeling / methods
LIM-Homeodomain Proteins
Mice
Mice, Transgenic
MicroRNAs / genetics
MicroRNAs / metabolism*
Neurons / cytology*
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
RNA, Untranslated / genetics
Retina / cytology
Retina / physiology
Retinal Cone Photoreceptor Cells / physiology*
Tissue Culture Techniques
Transcription Factors / metabolism*
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism

Substances

Homeodomain Proteins
LIM-Homeodomain Proteins
Lhx2 protein, mouse
MicroRNAs
Mirn124 microRNA, mouse
RNA, Small Interfering
RNA, Untranslated
Transcription Factors
Tumor Suppressor Proteins
prospero-related homeobox 1 protein