title: miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways.
abstract: Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways.
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR-7275, 660 route des Lucioles, 06560 Sophia-Antipolis, France.|University of Nice-Sophia-Antipolis (UNS), Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Valbonne, 06560 Sophia-Antipolis, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Chevalier
authors.affiliation: Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Adamiok
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR-7275, 660 route des Lucioles, 06560 Sophia-Antipolis, France.|University of Nice-Sophia-Antipolis (UNS), Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Valbonne, 06560 Sophia-Antipolis, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mercey
authors.affiliation: Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille, France.
authors.forename: Diego R
authors.initials: DR
authors.lastname: Revinski
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR-7275, 660 route des Lucioles, 06560 Sophia-Antipolis, France.|University of Nice-Sophia-Antipolis (UNS), Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Valbonne, 06560 Sophia-Antipolis, France.
authors.forename: Laure-Emmanuelle
authors.initials: LE
authors.lastname: Zaragosi
authors.affiliation: Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pasini
authors.affiliation: Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kodjabachian
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR-7275, 660 route des Lucioles, 06560 Sophia-Antipolis, France.|University of Nice-Sophia-Antipolis (UNS), Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Valbonne, 06560 Sophia-Antipolis, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.affiliation: CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR-7275, 660 route des Lucioles, 06560 Sophia-Antipolis, France.|University of Nice-Sophia-Antipolis (UNS), Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Valbonne, 06560 Sophia-Antipolis, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Marcet
mesh_terms: D000199:Actins / Q000378:metabolism*; D000354:Africa, Western; D000818:Animals; D064652:Basal Bodies / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D000066630:Ectopic Gene Expression; D004625:Embryo, Nonmammalian; D042783:Endothelial Cells / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D064448:Filamins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000235:genetics*; D018613:Microscopy, Confocal; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology; D060888:Real-Time Polymerase Chain Reaction; D014982:Xenopus laevis; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D064448:Filamins; C522425:MIRN34 microRNA, human; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; C085929:RRAS protein, human; D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins