![]() ![]() tropicalis mucociliary epidermis develops after gastrulation, with postmitotic multiciliated cells (MCC) and multiciliary bundles beating in a polarized direction to generate fluid flow from head to tail of the embryo that removes pathogens and aids oxygenation (Supplementary Movie 1– 4). tropicalis motile cilia formation requires Wnt/Gsk3 signaling ![]() Here, we reveal that motile cilia are Wnt signaling organelles that transduce a distinct Wnt ┫Pp1 response, with implications for the cell biology of Wnt signaling, cilia formation and function, and for new therapeutic avenues to ciliopathies. Mammalian airway epithelia and the surface of Xenopus embryos are highly similar in cell composition and function, which has made Xenopus a model of choice for investigating novel regulatory mechanisms for motile cilia function and ciliopathy related phenotypes 17. tropicalis (frog) embryos, a well-established model to study the development and function of mucociliary epithelia. To investigate the possibility of Wnt signaling in motile cilia, we used the embryonic skin of X. Flagellar Wnt signaling raises the provocative question: Are motile cilia Wnt-transducing organelles? If so, what response do they trigger and to what end? Wnt signaling across the flagellar outer membrane is intriguing because unlike chemosensory primary cilia, motile cilia are with few exceptions 15, 16 considered as signaling-inert nanomotors. This is also the case in spermatozoa, where Wnt/Gsk3 signaling orchestrates a rich post-transcriptional flagellar morphogenesis program 5. Ccnyl1 and its close homolog Cyclin Y (Ccny) activate CDK14/16, which phosphorylate and prime the Wnt co-receptor LRP6 (low-density lipoprotein receptor-related protein 6) for incoming Wnt ligands mostly in β-catenin-independent Wnt/Gsk3 signaling 13, 14. However, the function of Wnt/Ccnyl1 in sperm flagellar morphogenesis is independent of β-catenin and transcription. In addition, Wnt/β-catenin signaling promotes motile ciliogenesis in zebrafish, frog, and mouse via transcriptional gene activation of downstream regulators such as the transcription factor Foxj1 7, 8, 9, 10, 11, 12. ![]() Cyclin Y-like 1 ( Ccnyl1) mutant mice are male sterile 5, 6 and we elucidated that this is because Wnt signaling across the flagellar outer membrane is required to promote sperm maturation 5. Deficiency of these nanopropellers leads to airway disease and ciliopathies 3, and understanding their cell biology is important for the rational design of cilio-stimulatory therapies 4.Ī highly specialized form of motile cilia are flagella of spermatozoa. In processes ranging from larval development to respiration, mucociliary membranes defend epithelia against irritants and pathogens by a directional mucous flow generated through the coordinated beating of motile cilia 1, 2. tropicalis motile cilia are Wnt signaling organelles that transduce a distinct Wnt-Pp1 response. tropicalis ciliopathy models of male infertility and primary ciliary dyskinesia ( ccdc108, gas2l2). Moreover, Wnt treatment improves ciliary function in X. tropicalis embryos and primary human airway mucociliary epithelia. Wnt treatment stimulates ciliary beating in X. ![]() Live-cell imaging using a ciliary Gsk3 biosensor reveals an immediate response of motile cilia to Wnt ligand. Mucociliary Wnt signaling is essential for ciliogenesis and it engages Lrp6 co-receptors that localize to cilia via a VxP ciliary targeting sequence. Instead, it engages a Wnt-Gsk3-Ppp1r11-Pp1 signaling axis. tropicalis embryos that motile cilia transduce a ciliary Wnt signal that is distinct from canonical β-catenin signaling. Contrasting both views, we here show in the mucociliary epidermis of X. It is widely thought that Wnt/Lrp6 signaling proceeds through the cytoplasm and that motile cilia are signaling-inert nanomotors. ![]()
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