The role of ciliary Wnt signaling

• Applicants: Professor Christof Niehrs, Ph.D.; Professor Dr. Heymut Omran
• Subject Area: Pneumology, Thoracic Surgery ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561925426

Ciliopathies play a prominent role in respiratory diseases.We recently reported that primary and motile cilia are Wnt signaling organelles, which transduce through a novel, non-transcriptional pathway to regulate ciliogenesis and ciliary beat frequency (CBF). This grant proposal aims to elucidate the physiological processes and tissues in which primary and mucociliary Wnt signaling play is involved in mice. By specifically focusing on a separation-of-function mutant for the Wnt co-receptor LRP6 (Lrp6-CTS mutant), the study seeks to differentiate ciliary from non-ciliary Wnt signaling. Validation of the Lrp6-CTS mutant will involve the analysis of Lrp6 protein localization in mouse embryonic fibroblasts, responsiveness to WNT3A, and potential cilia defects. Lrp6-CTS mutant mice will be closely examined for defects in organs with prominent ciliary/mucociliary function, such as the neural tube, respiratory tract, kidney, and eye. Lrp6-CTS mutant airway epithelia will be analyzed for CBF. The study will also evaluate the impact of different Wnts and pharmacological Wnt pathway inhibitors on CBF and differentiation of airway epithelia in both wildtype and Lrp6-CTS-/- mice, offering insights into ligand specificity and potential pharmacological stimulation of CBF. By addressing these questions through the proposed experimental approach, a thorough exploration of the physiological role of ciliary Wnt signaling will be achieved, contributing to our understanding of Wnt and cilia cell biology as well as ciliopathies.

• DFG Programme: Research Grants