Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, United States of America.
Department of Cell and Developmental Biology, Medical School, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2024 Jun 7;19(6):e0294835. doi: 10.1371/journal.pone.0294835. eCollection 2024.
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.
刺猬 (HH) 途径调节胚胎发育的舌前味蘑菇状 (FP) 和后舌环 (CVP) 和叶状 (FOP) 味觉蘑菇。HH 信号也介导成年味觉器官的维持和再生。然而，在出生后味觉器官分化和成熟过程中，HH 途径成分的表达存在知识空白。重要的是，HH 转录效应物 GLI1、GLI2 和 GLI3 尚未在出生后早期阶段进行研究;HH 受体 PTCH1、GAS1、CDON 和 HHIP，需要驱动 HH 途径的激活或拮抗作用，也尚未得到探索。使用 lacZ 报告基因小鼠模型，我们在早期和晚期出生后和成年阶段的 FP、CVP 和 FOP 中绘制了 HH 配体 SHH、HH 受体和 GLI 转录因子的表达图谱。在成年阶段，我们还研究了软腭，以及神经节和三叉神经节，它们向舌前延伸传入纤维。Shh 和 Gas1 是唯一在所有三种蘑菇和软腭的味觉蘑菇中一致表达的成分。在出生后的第一周，我们观察到 HH 信号成分在 FP 和相邻的非味觉丝状 (FILIF) 蘑菇的上皮或基质和舌肌中广泛表达。值得注意的是，我们观察到 Gli1 在 FILIF 和 Gas1 在肌肉中的消除，以及 Ptch1 在舌上皮和 Cdon、Gas1 和 Hhip 在基质中的下调，从晚期出生后阶段开始。此外，CVP 和 FOP 上皮中的 HH 受体表达模式与前 FP 不同。在所有的成分中，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。我们的研究强调了 HH 信号在不同出生后发育阶段和前舌与后舌味觉器官中的差异调节，并为理解 HH 信号众多成分在出生后舌发育中的作用的功能研究奠定了基础。
