Flattop regulates basal body docking and positioning in mono- and multiciliated cells
Moritz Gegg,
Anika Böttcher,
Ingo Burtscher,
Stefan Hasenoeder,
Claude Van Campenhout,
Michaela Aichler,
Axel Walch,
Seth G N Grant,
Heiko Lickert
Affiliations
Moritz Gegg
Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Munich, Germany
Anika Böttcher
Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Munich, Germany
Ingo Burtscher
Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Munich, Germany
Stefan Hasenoeder
Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Munich, Germany
Claude Van Campenhout
Genetique du Developpement, L'Institut de biologie et de médecine moléculaires, Université libre de Bruxelles, Gosselies, Belgium
Michaela Aichler
Research Unit Analytical Pathology, Helmholtz Center Munich, Munich, Germany
Axel Walch
Research Unit Analytical Pathology, Helmholtz Center Munich, Munich, Germany
Seth G N Grant
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom; Centre for Neuroregeneration, Univeristy of Edinburgh, Cambridge, United Kingdom
Heiko Lickert
Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany; Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Munich, Germany
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.
