Department of Anatomy and Cell Biology, The Kidney Institute, University of Kansas Medical Center, Kansas City, KS, USA.
Wiley Interdiscip Rev Syst Biol Med. 2013 Jan-Feb;5(1):83-100. doi: 10.1002/wsbm.1193. Epub 2012 Oct 11.
The Hedgehog (Hh) signaling pathway plays a fundamental role in development and tissue homeostasis, governing cell proliferation and differentiation, as well as cell fate. Hh signaling is mediated by an intricate network of proteins that have positive and negative roles that work in concert to fine-tune signaling output. Using feedback loops, redundancy and subcellular compartmentalization, the temporal and spatial dynamics of Hh signaling have evolved to be complex and robust. Yet developmental defects and cancers that arise from perturbation of the Hh pathway reflect specific pathway fragilities. Importantly, these fragile nodes and edges present opportunities for the design of targeted therapies. Despite these significant advances, unconnected molecular links within the Hh pathway still remain, many of which revolve around the dependence of Hh signaling on the primary cilium, an antenna-like sensory organelle. A systems-level understanding of Hh signaling and of ciliary biology will comprehensively define all nodes and edges of the Hh signaling network and will help identify precise therapeutic targets.
刺猬（Hh）信号通路在发育和组织稳态中起着至关重要的作用，调控着细胞增殖和分化以及细胞命运。Hh 信号由一个复杂的蛋白质网络介导，这些蛋白质具有正、负两种作用，协同工作以精细调节信号输出。通过反馈回路、冗余和亚细胞区室化，Hh 信号的时空动力学已经进化得非常复杂和稳健。然而，由于 Hh 途径的扰动而产生的发育缺陷和癌症，反映了特定途径的脆弱性。重要的是，这些脆弱的节点和边缘为靶向治疗的设计提供了机会。尽管取得了这些重大进展，但 Hh 途径中仍然存在未连接的分子链接，其中许多都与 Hh 信号依赖于初级纤毛有关，初级纤毛是一种类似天线的感觉细胞器。对 Hh 信号和纤毛生物学的系统水平理解将全面定义 Hh 信号网络的所有节点和边缘，并有助于确定精确的治疗靶点。
