Flattop regulates basal body docking and positioning in mono- and multiciliated cells

  1. Moritz Gegg
  2. Anika Böttcher
  3. Ingo Burtscher
  4. Stefan Hasenöder
  5. Claude Van Campenhout
  6. Michaela Aichler
  7. Axel Walch
  8. Seth G. N. Grant
  9. Heiko Lickert  Is a corresponding author
  1. Helmholtz Center Munich, Germany
  2. Université libre de Bruxelles, Belgium
  3. University of Edinburgh, United Kingdom

Abstract

Planar cell polarity (PCP) regulates basal body (BB) docking and positioning during cilia formation, but the underlying mechanisms remain elusive. Here, 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 at 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.

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Author details

  1. Moritz Gegg

    Helmholtz Center Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Anika Böttcher

    Helmholtz Center Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Ingo Burtscher

    Helmholtz Center Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Stefan Hasenöder

    Helmholtz Center Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Claude Van Campenhout

    Université libre de Bruxelles, Gosselies, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Michaela Aichler

    Helmholtz Center Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Axel Walch

    Helmholtz Center Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Seth G. N. Grant

    University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Heiko Lickert

    Helmholtz Center Munich, Munich, Germany
    For correspondence
    heiko.lickert@helmholtz-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Mouse keeping was done at the central facilities at HMGU in accordance with the German animal welfare legislation and acknowledged guidelines of the Society of Laboratory Animals (GV-SOLAS) and of the Federation of Laboratory Animal Science Associations (FELASA). Post-mortem examination of organs was not subject to regulatory authorization.

Copyright

© 2014, Gegg et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Moritz Gegg
  2. Anika Böttcher
  3. Ingo Burtscher
  4. Stefan Hasenöder
  5. Claude Van Campenhout
  6. Michaela Aichler
  7. Axel Walch
  8. Seth G. N. Grant
  9. Heiko Lickert
(2014)
Flattop regulates basal body docking and positioning in mono- and multiciliated cells
eLife 3:e03842.
https://doi.org/10.7554/eLife.03842

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https://doi.org/10.7554/eLife.03842