Mucociliary Wnt signaling promotes cilia biogenesis and beating

Carina Seidl, Fabio Silva, Kaiqing Zhang, Kai Wohlgemuth, Heymut Omran and Christof Niehrs ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36743-2

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