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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish
Article numbere03842
JournaleLife
Volume3
DOIs
StatePublished - 8 Oct 2014
Externally publishedYes

Keywords

  • Flattop
  • actin
  • basal body
  • cell biology
  • developmental biology
  • microtubule
  • mouse
  • planar cell polarity
  • spindle positioning
  • stem cells

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