title: Mir-17-3p controls spinal neural progenitor patterning by regulating Olig2/Irx3 cross-repressive loop.
abstract: Neural patterning relies on transcriptional cross-repressive interactions that ensure unequivocal assignment of neural progenitor identity to proliferating cells. Progenitors of spinal motor neurons (pMN) and V2 interneurons (p2) are specified by a pair of cross-repressive transcription factors, Olig2 and Irx3. Lineage tracing revealed that many p2 progenitors transiently express the pMN marker Olig2 during spinal cord development. Here we demonstrate that the repression of Olig2 in p2 domain is controlled by mir-17-3p microRNA-mediated silencing of Olig2 mRNA. Mice lacking all microRNAs or just the mir-17∼92 cluster manifest a dorsal shift in pMN/p2 boundary and impairment in the production of V2 interneurons. Our findings suggest that microRNA-mediated repression of Olig2 mRNA plays a critical role during the patterning of ventral spinal progenitor domains by shifting the balance of cross-repressive interactions between Olig2 and Irx3 transcription factors.
authors.affiliation: Departments of Pathology and Cell Biology, Neurology, and Neuroscience, Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Jun-An
authors.initials: JA
authors.lastname: Chen
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Huang
authors.forename: Esteban O
authors.initials: EO
authors.lastname: Mazzoni
authors.forename: G Christopher
authors.initials: GC
authors.lastname: Tan
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.forename: Hynek
authors.initials: H
authors.lastname: Wichterle
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D004622:Embryo, Mammalian; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D046911:Macromolecular Substances / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000502:physiology*; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D000076104:Oligodendrocyte Transcription Factor 2; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D043244:Ribonuclease III; D013116:Spinal Cord / Q000166:cytology*; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053487:DEAD-box RNA Helicases; D004318:Doxycycline; D004722:Endoribonucleases; D004965:Estrogen Antagonists; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011506:Proteins; D022661:RNA, Untranslated; D043244:Ribonuclease III; D013629:Tamoxifen; D014157:Transcription Factors; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C501599:Irx3 protein, mouse; C543614:Mirn17 microRNA, mouse; C491328:Nkx6-1 protein, mouse; C512773:Olig2 protein, mouse; C016601:afimoxifene; C509781:Dicer1 protein, mouse