Moritz Gegg1, Anika Böttcher1, Ingo Burtscher1, Stefan Hasenoeder1, Claude Van Campenhout2, Michaela Aichler3, Axel Walch3, Seth G N Grant4, Heiko Lickert1. 1. Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany. 2. Genetique du Developpement, L'Institut de biologie et de médecine moléculaires, Université libre de Bruxelles, Gosselies, Belgium. 3. Research Unit Analytical Pathology, Helmholtz Center Munich, Munich, Germany. 4. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
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.
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 pan class="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: Mireille Montcouquiol; Rivka A Rachel; Pamela J Lanford; Neal G Copeland; Nancy A Jenkins; Matthew W Kelley Journal: Nature Date: 2003-04-30 Impact factor: 49.962
Authors: Erik Bader; Adriana Migliorini; Moritz Gegg; Noah Moruzzi; Jantje Gerdes; Sara S Roscioni; Mostafa Bakhti; Elisabeth Brandl; Martin Irmler; Johannes Beckers; Michaela Aichler; Annette Feuchtinger; Christin Leitzinger; Hans Zischka; Rui Wang-Sattler; Martin Jastroch; Matthias Tschöp; Fausto Machicao; Harald Staiger; Hans-Ulrich Häring; Helena Chmelova; Julie A Chouinard; Nikolay Oskolkov; Olle Korsgren; Stephan Speier; Heiko Lickert Journal: Nature Date: 2016-07-11 Impact factor: 49.962
Authors: Jason R Cowan; Muhammad Tariq; Chad Shaw; Mitchell Rao; John W Belmont; Seema R Lalani; Teresa A Smolarek; Stephanie M Ware Journal: Philos Trans R Soc Lond B Biol Sci Date: 2016-12-19 Impact factor: 6.237