title: Flattop regulates basal body docking and positioning in mono- and multiciliated cells.
abstract: Planar cell polarity (PCP) regulates basal body (BB) docking and positioning during cilia formation, but the underlying mechanisms remain elusive. In this study, we investigate the uncharacterized gene Flattop (Fltp) that is transcriptionally activated during PCP acquisition in ciliated tissues. Fltp knock-out mice show BB docking and ciliogenesis defects in multiciliated lung cells. Furthermore, Fltp is necessary for kinocilium positioning in monociliated inner ear hair cells. In these cells, the core PCP molecule Dishevelled 2, the BB/spindle positioning protein Dlg3, and Fltp localize directly adjacent to the apical plasma membrane, physically interact and surround the BB at the interface of the microtubule and actin cytoskeleton. Dlg3 and Fltp knock-outs suggest that both cooperatively translate PCP cues for BB positioning in the inner ear. Taken together, the identification of novel BB/spindle positioning components as potential mediators of PCP signaling might have broader implications for other cell types, ciliary disease, and asymmetric cell division.
authors.affiliation: Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Gegg
authors.affiliation: Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Böttcher
authors.affiliation: Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Burtscher
authors.affiliation: Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hasenoeder
authors.affiliation: Genetique du Developpement, L'Institut de biologie et de médecine moléculaires, Université libre de Bruxelles, Gosselies, Belgium.
authors.forename: Claude
authors.initials: C
authors.lastname: Van Campenhout
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Center Munich, Munich, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Aichler
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Center Munich, Munich, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Seth G N
authors.initials: SG
authors.lastname: Grant
authors.affiliation: Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D064652:Basal Bodies / Q000378:metabolism* / Q000648:ultrastructure; D001665:Binding Sites; D016764:Cell Polarity; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D017124:Conserved Sequence; D007758:Ear, Inner / Q000378:metabolism / Q000648:ultrastructure; D017930:Genes, Reporter; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism; D008168:Lung / Q000473:pathology; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059547:Stereocilia / Q000378:metabolism / Q000648:ultrastructure; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D000199:Actins; C000598970:Flattop protein, mouse; C496503:Foxa2 protein, mouse; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011506:Proteins; D051542:Hepatocyte Nuclear Factor 3-beta
keywords: Flattop; actin; basal body; cell biology; developmental biology; microtubule; mouse; planar cell polarity; spindle positioning; stem cells