Genetic regulation of Wnt/PCP components through Fgf10/Fgfr2/Sox9 module in tear duct development

Fibroblast growth factor (Fgf) and Wnt signaling pathways are essential for diverse aspects of tissue morphogenesis, and their disruption often results in overlapping developmental defects. However, the mechanistic links between these pathways remain poorly defined, and it is unclear whether direct genetic interactions exist during development. In this study, we demonstrate that the Fgf signaling components Fgf10 and Fgfr2 are indispensable for tear duct formation by promoting the proliferation and survival of tear duct progenitors. In addition, Fgf10/Fgfr2 signaling contributes to tear duct elongation. Through single-cell RNA sequencing and CUT&Tag analysis, we provide comprehensive genetic evidence that the Fgf10/Fgfr2/Sox9 module directly regulates a subset of Wnt/planar cell polarity (PCP) genes. In particular, we show that Sox9 binds to and activates the promoter of Prickle1, a core Wnt/PCP component previously implicated in tear duct development. Finally, we establish that the regulation of Wnt/PCP components by Fgf signaling is unidirectional. Together, these findings uncover a previously unrecognized direct genetic link between Fgf signaling and Wnt/PCP pathway components during tear duct morphogenesis.