title: MiR-29b controls fetal mouse neurogenesis by regulating ICAT-mediated Wnt/β-catenin signaling.
abstract: β-Catenin has been widely implicated in the regulation of mammalian development and cellular homeostasis. However, the mechanisms by which Wnt/β-catenin signaling components regulate physiological events during brain development remain undetermined. Inactivation of glycogen synthase kinase (GSK)-3β leads to β-catenin accumulation in the nucleus, where it couples with T-cell factor (TCF), an association that is disrupted by ICAT (inhibitor of β-catenin and T cell factor). In this study, we sought to determine whether regulation of ICAT by members of the microRNA-29 family plays a role during neurogenesis and whether deregulation of ICAT results in defective neurogenesis due to impaired β-catenin-mediated signaling. We found that miR-29b, but not miR-29a or 29c, is significantly upregulated in three-dimensionally cultured neural stem cells (NSCs), whereas ICAT is reduced as aged. Treatment with a miR-29b reduced the reporter activity of a luciferase-ICAT 3'-UTR construct whereas a control (scrambled) miRNA oligonucleotide did not, indicating that miR-29b directly targets the 3'-UTR of ICAT. We also found that treatment with miR-29b diminished NSC self-renewal and proliferation, and controlled their fate, directing their differentiation along certain cell lineages. Furthermore, our in vivo results showed that inhibition of miR-29b by in utero electroporation induced a profound defect in corticogenesis during mouse development. Taken together, our results demonstrate that miR-29b plays a pivotal role in fetal mouse neurogenesis by regulating ICAT-mediated Wnt/β-catenin signaling.
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehakro, Jongro-gu, Seoul 110-799, South Korea.
authors.forename: J
authors.initials: J
authors.lastname: Shin
authors.affiliation: School of Mechanical Engineering, Korea University, Seoul 136-713, South Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: S-M
authors.initials: SM
authors.lastname: Oh
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehakro, Jongro-gu, Seoul 110-799, South Korea.
authors.forename: W-J
authors.initials: WJ
authors.lastname: Yu
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: J-P
authors.initials: JP
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: S-O
authors.initials: SO
authors.lastname: Huh
authors.affiliation: Department of Neurosurgery, Boramae Hospital, Seoul National University, Dongjakku, Seoul 156-707, South Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: 1] Department of Pharmacology and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehakro, Jongro-gu, Seoul 110-799, South Korea [2] Korea Brain Research Institute (KBRI), Daegu 700-010, South Korea.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Suh
authors.affiliation: School of Mechanical Engineering, Korea University, Seoul 136-713, South Korea.
authors.forename: S
authors.initials: S
authors.lastname: Chung
authors.affiliation: 1] Department of Pharmacology and Biomedical Sciences, Seoul National University, College of Medicine, 103 Daehakro, Jongro-gu, Seoul 110-799, South Korea [2] Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Sungnam 463-707, South Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C498785:Ctnnbip1 protein, mouse; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D012097:Repressor Proteins; D051176:beta Catenin