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Abstract：
The Hedgehog (HH) pathway regulates embryonic development of anterior tongue taste fungiform papilla (FP) and the posterior circumvallate (CVP) and foliate (FOP) taste papillae. HH signaling also mediates taste organ maintenance and regeneration in adults. However, there are knowledge gaps in HH pathway component expression during postnatal taste organ differentiation and maturation. Importantly, the HH transcriptional effectors GLI1, GLI2 and GLI3 have not been investigated in early postnatal stages; the HH receptors PTCH1, GAS1, CDON and HHIP, required to either drive HH pathway activation or antagonism, also remain unexplored. Using lacZ reporter mouse models, we mapped expression of the HH ligand SHH, HH receptors, and GLI transcription factors in FP, CVP and FOP in early and late postnatal and adult stages. In adults we also studied the soft palate, and the geniculate and trigeminal ganglia, which extend afferent fibers to the anterior tongue. Shh and Gas1 are the only components that were consistently expressed within taste buds of all three papillae and the soft palate. In the first postnatal week, we observed broad expression of HH signaling components in FP and adjacent, non-taste filiform (FILIF) papillae in epithelium or stroma and tongue muscles. Notably, we observed elimination of Gli1 in FILIF and Gas1 in muscles, and downregulation of Ptch1 in lingual epithelium and of Cdon, Gas1 and Hhip in stroma from late postnatal stages. Further, HH receptor expression patterns in CVP and FOP epithelium differed from anterior FP. Among all the components, only known positive regulators of HH signaling, SHH, Ptch1, Gli1 and Gli2, were expressed in the ganglia. Our studies emphasize differential regulation of HH signaling in distinct postnatal developmental periods and in anterior versus posterior taste organs, and lay the foundation for functional studies to understand the roles of numerous HH signaling components in postnatal tongue development.
摘要：
Hedgehog（HH）通路调节前舌味觉菌状乳头（FP）和后旋（CVP）和叶状（FOP）味觉乳头的胚胎发育。HH信号传导还介导成人的味觉器官维持和再生。然而,在出生后味觉器官分化和成熟过程中，HH途径成分表达存在知识空白。重要的是,HH转录效应子GLI1、GLI2和GLI3尚未在出生后早期进行研究；HH受体PTCH1、GAS1、CDON和HHIP，需要驱动HH途径激活或拮抗，也仍未探索。使用lacZ记者小鼠模型，我们定位了HH配体SHH的表达，HH受体,和FP中的GLI转录因子，出生后早期和晚期以及成人阶段的CVP和FOP。在成年人中，我们还研究了软腭，膝状和三叉神经节，将传入纤维延伸到前舌。Shh和Gas1是在所有三个乳头和软腭的味蕾中一致表达的唯一成分。在产后第一周，我们观察到HH信号传导成分在FP和邻近的广泛表达，上皮或间质和舌肌的无味丝状（FILIF）乳头。值得注意的是,我们观察到肌肉中FILIF和Gas1中Gli1的消除，舌上皮和Cdon中Ptch1的下调，产后晚期基质中的Gas1和Hip。Further,CVP和FOP上皮中的HH受体表达模式与前FP不同。在所有组件中，只有已知的HH信号的正调节剂，SHH,Ptch1，Gli1和Gli2在神经节中表达。我们的研究强调HH信号在不同的出生后发育期和前后味觉器官中的差异调节，并为功能研究奠定基础，以了解众多HH信号传导成分在出生后舌发育中的作用。
