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

被引：241

作者：

Sanuki, Rikako ^{[1
,2
]}

Onishi, Akishi ^{[1
,2
]}

Koike, Chieko ^{[1
]}

Muramatsu, Rieko ^{[3
]}

Watanabe, Satoshi ^{[1
,2
]}

Muranishi, Yuki ^{[1
]}

Irie, Shoichi ^{[1
,2
]}

Uneo, Shinji ^{[4
]}

Koyasu, Toshiyuki ^{[4
]}

Matsui, Ryosuke ^{[5
]}

Cherasse, Yoan ^{[6
]}

Urade, Yoshihiro ^{[6
]}

Watanabe, Dai ^{[5
]}

Kondo, Mineo ^{[4
]}

Yamashita, Toshihide ^{[3
]}

Furukawa, Takahisa ^{[1
,2
]}

机构：

[1] Osaka Biosci Inst, Dept Dev Biol, Osaka, Japan

[2] Japan Sci & Technol Agcy, Osaka Biosci Inst, Osaka, Japan

[3] Osaka Univ, Grad Sch Med, Dept Mol Neurosci, Osaka, Japan

[4] Nagoya Univ, Dept Ophthalmol, Grad Sch Med, Showa Ku, Nagoya, Aichi 4648601, Japan

[5] Kyoto Univ, Dept Biol Sci, Fac Med, Grad Sch Biostudies,Sakyo Ku, Kyoto, Japan

[6] Osaka Biosci Inst, Dept Mol Behav Biol, Osaka, Japan

来源：

NATURE NEUROSCIENCE | 2011年 / 14卷 / 09期

基金：

日本科学技术振兴机构;

关键词：

DEVELOPING MOUSE RETINA; HOMEOBOX GENE; CELL FATE; TRANSCRIPTION FACTORS; EARLY NEUROGENESIS; MICRORNA TARGETS; TRANSGENIC MICE; MESSENGER-RNAS; DIFFERENTIATION; EXPRESSION;

D O I：

10.1038/nn.2897

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1125 / U177

页数：12

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