title: MicroRNA-124 Regulates Cell Specification in the Cochlea through Modulation of Sfrp4/5.
abstract: The organ of Corti, the auditory organ of the mammalian inner ear, contains sensory hair cells and supporting cells that arise from a common sensory progenitor. The molecular bases allowing the specification of these progenitors remain elusive. In the present study, by combining microarray analyses with conditional deletion of Dicer in the developing inner ear, we identified that miR-124 controls cell fate in the developing organ of Corti. By targeting secreted frizzled-related protein 4 (Sfrp4) and Sfrp5, two inhibitors of the Wnt pathway, we showed that miR-124 controls the β-catenin-dependent and also the PCP-related non-canonical Wnt pathways that contribute to HC differentiation and polarization in the organ of Corti. Thus, our work emphasizes the importance of miR-124 as an epigenetic safeguard that fine-tunes the expression of genes critical for cell patterning during cochlear differentiation.
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Huyghe
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Van den Ackerveken
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Sacheli
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Prévot
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Thelen
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Justine
authors.initials: J
authors.lastname: Renauld
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Thiry
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Delacroix
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
authors.affiliation: GIGA-Neurosciences, University of Liege, C.H.U. Sart Tilman, Liege 4000, Belgium. Electronic address: bmalgrange@ulg.ac.be.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malgrange
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics; D004622:Embryo, Mammalian; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007760:Labyrinth Supporting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D038081:Organogenesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D053487:DEAD-box RNA Helicases; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D043244:Ribonuclease III; D055748:SOXB1 Transcription Factors; D051176:beta Catenin; C495267:CTNNB1 protein, mouse; C540079:Mirn124 microRNA, mouse; C498454:Sfrp4 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C487972:Sfrp5 protein, mouse; C527783:Sox2 protein, mouse; C509781:Dicer1 protein, mouse