Ablation of NTPDase2+cells inhibits the formation of filiform papillae in tongue tip

Feng Li; Bo-Wen Niu; Meng-Min Zhu

doi:10.1002/ame2.12021

摘要：Background: Lingual epithelia in the tongue tip are among the most rapidly regener-ating tissues, but the mechanism of cell genesis in this tissue is still unknown. Previ-ous study has suggested the existence of multiple stem cell pools in lingual epithelia and papillae. Like K14+ and Sox2+ cells, NTPDase2+ cells have characteristics of stem cells. Methods: We employed a system using doxycycline to conditionally ablate NTPDase2+ cells in lingual epithelia and papillae by regulated expression of the diphtheria toxin A (DTA) gene. Transgenic lines, which expressed the rtTA gene in NTPDase2+ cells, were produced by pronuclear injection of zygotes from C57BL/6 mice using the BAC clone RP23-47P18. The NTPDase2-rtTA transgenic mice were crossed with the TetO-DTA transgenic animals. The double transgenic mice were treated with doxycycline. Doxycycline (Dox) was diluted in 5％ sucrose in water to a final concentration of 0.3-0.5 mg/mL and supplied as drinking water. Results: After 15 days of Dox induction, the expression of NTPDase2, Sox2 and K14 was ablated from lingual epithelia. DTA expression in NTPDase2+cells did not inhibit the turnover of GNAT3+ or PLCb2+ cells in taste buds, nor the expression of S100b beneath lingual epithelia and papillae. After 35 days ablation of NTPDase2+ cells, the basic structure of lingual epithelia and papillae remained intact. However, the ratio of cell to total tissue area was decreased in lingual epithelia and circumvallate (CV) papillae. DTA expres-sion also inhibited the regeneration of filiform papillae on the dorsal surface of the tongue tip. Conclusions: These studies provide important insights into the understanding of dynamic equilibrium among the multiple stem cell populations present in the lingual epithelia and papillae.