Summary: The aims of this study were to distinguish between the primary and secondary effects of TGF-β signalling disruption by Dox treatment in NTPDase2+ cells; and to investigate the interactions between TGF-β signalling and Jagged2/Notch1 pathway in regulating the expansion of tongue epithelia stem cells.
Transgenic mice expressing rtTA from the mouse NTPDase2 promoter or K14 promoter were used to generate an inducible dominant negative TGF-β receptor type II (Tgfbr2) mutant model.
Disruption of TGF-β signalling in NTPDase2+ cells initially inhibited the formation of filiform papillae but led to their regeneration over time. In contrast, disruption of TGF-β signalling induced proliferation of lingual epithelia in the middle tongue. We also observed the proliferation of lingual epithelia in the posterior tongue near the circumvallate papillae. Interactions among the TGF-β signalling pathways, Jagged2/Notch1 signalling pathways and epigenetic modifications regulate the expansion of lingual epithelial stem cells.
Different molecular mechanisms are involved in the developmental regulation of lingual epithelia and filiform papillae, dependent on the location along the whole tongue. The fluctuating phenotype of tongue epithelia, over time, may be the combined effects of signalling pathways and epigenetic modifications.