Abstract：
The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ). Losing Ihh results in cranial bone malformation and decreased ossification and affects the formation of cranial base cartilage unions, TMJ condyles, and joint discs. Gli1 is predominantly expressed during early craniofacial development, and Gli1+ cells are identified as the primary mesenchymal stem cells (MSCs) for craniofacial bones, crucial for cell differentiation and morphogenesis. In addition, a complex mutual regulatory mechanism exists between Gli1 and Ihh, ensuring the normal function of the Hh signaling pathway by directly or indirectly regulating each other\'s expression levels. And the interaction between Ihh and Gli1 significantly impacts the normal development of craniofacial tissues. This review summarizes the pivotal roles of Gli1 and Ihh in the intricate landscape of mammalian craniofacial development and outlines the molecular regulatory mechanisms and intricate interactions governing the growth of bone and cartilage exhibited by Gli1 and Ihh, which provides new insights into potential therapeutic strategies for related diseases or researches of tissue regeneration.
摘要：
Hedgehog（Hh）信号通路通过Hh蛋白的动态相互作用协调其影响，细胞表面受体Ptch1，Smo，和Gli转录因子，促成了无数的发展事件。IndianHedgehog（Ihh）和Gli锌指转录因子1（Gli1）在Hh信号通路的发育调控中起着至关重要的作用。Ihh调节软骨细胞增殖，分化,和骨骼形成，影响颅骨的发育，软骨，和颞下颌关节（TMJ）。失去Ihh会导致颅骨畸形，骨化减少，并影响颅底软骨结合的形成，TMJ髁,和联合圆盘。Gli1主要在早期颅面发育过程中表达，Gli1+细胞被鉴定为颅面骨的原代间充质干细胞（MSCs），对于细胞分化和形态发生至关重要。此外,Gli1和Ihh之间存在复杂的相互调节机制，通过直接或间接调节彼此的表达水平来保证Hh信号通路的正常功能。而Ihh与Gli1的相互作用显著影响颅面组织的正常发育。这篇综述总结了Gli1和Ihh在哺乳动物颅面发育的复杂景观中的关键作用，并概述了Gli1和Ihh表现出的控制骨骼和软骨生长的分子调节机制和复杂的相互作用，这为相关疾病或组织再生研究的潜在治疗策略提供了新的见解。
