Wnt/LRP6 signaling imbalance impairs ciliogenesis in human retina epithelial cells

The primary cilium is a microtubule-based organelle essential for various cellular functions, particularly signal transduction. While the role of cilia in regulating signaling pathways has been extensively studied, the impact of signaling pathways on cilia formation remains less well understood. Wnt signals are critical modulators of cell fate. In this study, we investigate how modulating Wnt signaling affects cilia formation in human retinal epithelial cells. Our findings show that enhancement of Wnt/LRP6 signaling before serum starvation impairs ciliogenesis. Cells with high baseline Wnt activity exhibited defective distal appendage formation, failure to remove CP110/CEP97 from mother centrioles, and reduced Rab8-vesicular docking, which are critical events for cilia membrane establishment and axoneme extension. Additionally, these cells displayed reduced autophagic flux, increased mTOR kinase activity, and elevated OFD1 levels at centriolar satellites. Importantly, mTOR inhibition rescued ciliogenesis in cells with elevated Wnt activity, underscoring the interplay between these signaling pathways. Our data also indicate that insufficient Wnt signaling activation disrupts ciliogenesis, emphasizing the need for precisely regulated Wnt levels.