Gaillard Dany, Bowles Spencer G, Salcedo Ernesto, Xu Mingang, Millar Sarah E, Barlow Linda A
Department of Cell & Developmental Biology and the Rocky Mountain Taste & Smell Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Departments of Dermatology and Cell & Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS Genet. 2017 Aug 28;13(8):e1006990. doi: 10.1371/journal.pgen.1006990. eCollection 2017 Aug.
Taste stimuli are transduced by taste buds and transmitted to the brain via afferent gustatory fibers. Renewal of taste receptor cells from actively dividing progenitors is finely tuned to maintain taste sensitivity throughout life. We show that conditional β-catenin deletion in mouse taste progenitors leads to rapid depletion of progenitors and Shh+ precursors, which in turn causes taste bud loss, followed by loss of gustatory nerve fibers. In addition, our data suggest LEF1, TCF7 and Wnt3 are involved in a Wnt pathway regulatory feedback loop that controls taste cell renewal in the circumvallate papilla epithelium. Unexpectedly, taste bud decline is greater in the anterior tongue and palate than in the posterior tongue. Mutant mice with this regional pattern of taste bud loss were unable to discern sweet at any concentration, but could distinguish bitter stimuli, albeit with reduced sensitivity. Our findings are consistent with published reports wherein anterior taste buds have higher sweet sensitivity while posterior taste buds are better tuned to bitter, and suggest β-catenin plays a greater role in renewal of anterior versus posterior taste buds.
味觉刺激由味蕾转导，并通过传入味觉纤维传递至大脑。来自活跃分裂祖细胞的味觉受体细胞更新受到精细调节，以在一生中维持味觉敏感性。我们发现，小鼠味觉祖细胞中条件性β-连环蛋白缺失会导致祖细胞和Shh+前体细胞迅速耗竭，进而导致味蕾丧失，随后味觉神经纤维丧失。此外，我们的数据表明LEF1、TCF7和Wnt3参与了一个Wnt信号通路调节反馈环，该反馈环控制轮廓乳头上皮中的味觉细胞更新。出乎意料的是，前舌和腭部的味蕾衰退比后舌更严重。具有这种区域性味蕾丧失模式的突变小鼠无法辨别任何浓度的甜味，但能够区分苦味刺激，尽管敏感性有所降低。我们的发现与已发表报告一致，即前味蕾对甜味的敏感性更高，而后味蕾对苦味的调节更好，这表明β-连环蛋白在前味蕾与后味蕾的更新中发挥着更大作用。
