Primary cilia and intraflagellar transport (IFT) proteins control a wide variety of processes duringdevelopment and tissue homeostasis. However, their potential roles in the regulation of stem celldifferentiation and tooth development remain elusive. Here, we uncovered the critical roles of ciliaryIFT80 in cilia formation and differentiation of dental pulp stem cells (DPSCs). IFT80-deficient DPSCsshowed reduced fibroblast growth factor receptor 1 (FGFR1) expression, leading to the disruption ofFGF2–FGFR1 signaling. We found, during DPSC differentiation, FGF2-FGFR1 signaling induces stressfiber rearrangement to promote cilia elongation, meanwhile stimulates PI3K-AKT signaling to aidHh/bone morphogenetic protein 2 (BMP2) signaling activation. These signaling pathways and theircoupling were disrupted in IFT80-deficient DPSCs, causing impaired differentiation. Our findings revealed a novel mechanism that ciliary protein regulates the odontogenic differentiation of DPSCs throughFGF/FGFR1 and Hh/BMP2 signaling

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