Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
Cells. 2021 May 30;10(6):1353. doi: 10.3390/cells10061353.
The Sonic hedgehog (Shh) molecular signaling pathway is well established as a key regulator of neurodevelopment. It regulates diverse cellular behaviors, and its functions vary with respect to cell type, region, and developmental stage, reflecting the incredible pleiotropy of this molecular signaling pathway. Although it is best understood for its roles in development, Shh signaling persists into adulthood and is emerging as an important regulator of astrocyte function. Astrocytes play central roles in a broad array of nervous system functions, including synapse formation and function as well as coordination and orchestration of CNS inflammatory responses in pathological states. Neurons are the source of Shh in the adult, suggesting that Shh signaling mediates neuron-astrocyte communication, a novel role for this multifaceted pathway. Multiple roles for Shh signaling in astrocytes are increasingly being identified, including regulation of astrocyte identity, modulation of synaptic organization, and limitation of inflammation. This review discusses these novel roles for Shh signaling in regulating diverse astrocyte functions in the healthy brain and in pathology.
Sonic hedgehog（Shh）分子信号通路是神经发育的关键调节剂，这一作用已得到充分证实。它调节着多种细胞行为，其功能因细胞类型、区域和发育阶段而异，反映了这一分子信号通路令人难以置信的多功能性。尽管 Shh 信号通路在发育过程中的作用最为人所熟知，但它在成年后仍然存在，并正在成为星形胶质细胞功能的重要调节剂。星形胶质细胞在广泛的神经系统功能中发挥着核心作用，包括突触形成和功能，以及在病理状态下协调和协调中枢神经系统炎症反应。神经元是成年期 Shh 的来源，这表明 Shh 信号转导介导神经元-星形胶质细胞通讯，这是该多效途径的一个新角色。Shh 信号在星形胶质细胞中的多种作用正逐渐被确定，包括调节星形胶质细胞的特性、调节突触组织以及限制炎症。本综述讨论了 Shh 信号在调节健康大脑和病理状态下星形胶质细胞多种功能方面的这些新作用。
