title: miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression.
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.
authors.affiliation: Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka, Japan.
authors.forename: Rikako
authors.initials: R
authors.lastname: Sanuki
authors.forename: Akishi
authors.initials: A
authors.lastname: Onishi
authors.forename: Chieko
authors.initials: C
authors.lastname: Koike
authors.forename: Rieko
authors.initials: R
authors.lastname: Muramatsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Muranishi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Irie
authors.forename: Shinji
authors.initials: S
authors.lastname: Uneo
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Koyasu
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Matsui
authors.forename: Yoan
authors.initials: Y
authors.lastname: Chérasse
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Dai
authors.initials: D
authors.lastname: Watanabe
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000002:abnormalities; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D018274:Electroporation / Q000379:methods; D004596:Electroretinography / Q000379:methods; D004622:Embryo, Mammalian; D005074:Evoked Potentials, Visual / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D020287:In Situ Nick-End Labeling / Q000379:methods; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein