title: MicroRNA-based silencing of Delta/Notch signaling promotes multiple cilia formation.
abstract: Multiciliated cells lining the surface of some vertebrate epithelia are essential for various physiological processes, such as airway cleansing. Their apical surface is constituted by hundreds of motile cilia, which beat in a coordinated manner to generate directional fluid flow. We recently reported the identification of microRNAs of the miR-449 family as evolutionary conserved key regulators of vertebrate multiciliogenesis. This novel function of miR-449 was established using in vivo and in vitro antisense approaches in two distinct experimental models. miR-449 strongly accumulated in multiciliated cells in human airway epithelium and Xenopus laevis embryonic epidermis, where it triggered centriole multiplication and multiciliogenesis by directly repressing the Delta/Notch pathway. Our data complement previous reports that showed the blocking action of miR-449 on the cell cycle, and unraveled a novel conserved mechanism whereby Notch signaling must undergo microRNA-mediated inhibition to permit differentiation of ciliated cell progenitors. We review here several important questions regarding the links between microRNAs and the Notch pathway in the control of cell fate.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Pharmacologie Moléculaire et Cellulaire, UMR-6097, Sophia-Antipolis, France. marcet@ipmc.cnrs.fr
authors.forename: Brice
authors.initials: B
authors.lastname: Marcet
authors.forename: Benoît
authors.initials: B
authors.lastname: Chevalier
authors.forename: Christelle
authors.initials: C
authors.lastname: Coraux
authors.forename: Laurent
authors.initials: L
authors.lastname: Kodjabachian
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D002502:Centrioles / Q000378:metabolism / Q000502:physiology; D002923:Cilia / Q000378:metabolism* / Q000502:physiology; D004817:Epidermis / Q000378:metabolism / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D037941:Silencer Elements, Transcriptional; D014981:Xenopus / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; C560106:DLL1 protein, Xenopus; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D036341:Intercellular Signaling Peptides and Proteins; C544530:MIRN449 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D029867:Xenopus Proteins