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Mucociliary Wnt signaling promotes cilia biogenesis and beating

Author

Listed:
  • Carina Seidl

    (DKFZ-ZMBH Alliance)

  • Fabio Silva

    (DKFZ-ZMBH Alliance)

  • Kaiqing Zhang

    (DKFZ-ZMBH Alliance)

  • Kai Wohlgemuth

    (University Children’s Hospital Muenster, Department of General Pediatrics)

  • Heymut Omran

    (University Children’s Hospital Muenster, Department of General Pediatrics)

  • Christof Niehrs

    (DKFZ-ZMBH Alliance
    Institute of Molecular Biology (IMB))

Abstract

It is widely thought that Wnt/Lrp6 signaling proceeds through the cytoplasm and that motile cilia are signaling-inert nanomotors. Contrasting both views, we here show in the mucociliary epidermis of X. tropicalis embryos that motile cilia transduce a ciliary Wnt signal that is distinct from canonical β-catenin signaling. Instead, it engages a Wnt-Gsk3-Ppp1r11-Pp1 signaling axis. Mucociliary Wnt signaling is essential for ciliogenesis and it engages Lrp6 co-receptors that localize to cilia via a VxP ciliary targeting sequence. Live-cell imaging using a ciliary Gsk3 biosensor reveals an immediate response of motile cilia to Wnt ligand. Wnt treatment stimulates ciliary beating in X. tropicalis embryos and primary human airway mucociliary epithelia. Moreover, Wnt treatment improves ciliary function in X. tropicalis ciliopathy models of male infertility and primary ciliary dyskinesia (ccdc108, gas2l2). We conclude that X. tropicalis motile cilia are Wnt signaling organelles that transduce a distinct Wnt-Pp1 response.

Suggested Citation

  • Carina Seidl & Fabio Silva & Kaiqing Zhang & Kai Wohlgemuth & Heymut Omran & Christof Niehrs, 2023. "Mucociliary Wnt signaling promotes cilia biogenesis and beating," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36743-2
    DOI: 10.1038/s41467-023-36743-2
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    References listed on IDEAS

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    1. Ann-Kathrin Volz & Alina Frei & Viola Kretschmer & António M. Jesus Domingues & Rene F. Ketting & Marius Ueffing & Karsten Boldt & Eva-Maria Krämer-Albers & Helen L. May-Simera, 2021. "Bardet-Biedl syndrome proteins modulate the release of bioactive extracellular vesicles," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    2. Gary Davidson & Wei Wu & Jinlong Shen & Josipa Bilic & Ursula Fenger & Peter Stannek & Andrei Glinka & Christof Niehrs, 2005. "Casein kinase 1 γ couples Wnt receptor activation to cytoplasmic signal transduction," Nature, Nature, vol. 438(7069), pages 867-872, December.
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