Signaling by Hedgehog

Hedgehog (Hh) is a secreted morphogen that regulates developmental processes in vertebrates including limb bud formation, neural tube patterning, cell growth and differentiation (reviewed in Hui and Angers, 2011). Hh signaling also contributes to stem cell homeostasis in adult tissues. Downregulation of Hh signaling can lead to neonatal abnormalities, while upregulation of signaling is associated with the development of various cancers (Beachy et al, 2004; Jiang and Hui, 2008; Hui and Angers, 2011).<br><br>Hh signaling is switched between 'off' and an 'on' states to differentially regulate an intracellular signaling cascade that targets the Gli transcription factors. In the absence of Hh ligand, cytosolic Gli proteins are cleaved to yield a truncated form that translocates into the nucleus and represses target gene transcription. Binding of Hh to the Patched (PTC) receptor on the cell surface stabilizes the Gli proteins in their full-length transcriptional activator form, stimulating Hh-dependent gene expression (reviewed in Hui and Angers, 2011; Briscoe and Therond, 2013).<br><br>

刺猬因子（Hh）是一种分泌型形态发生素，调控脊椎动物发育过程中的多项生理过程，包括肢体芽的形成、神经管模式构建、细胞增殖与分化（参见 Hui 和 Angers，2011 年综述）。Hh 信号传导还参与维持成年组织中干细胞的稳态。Hh 信号传导的下调可能导致新生儿畸形，而信号传导的上调则与多种癌症的发生发展相关（参见 Beachy 等人，2004 年；Jiang 和 Hui，2008 年；Hui 和 Angers，2011 年）。Hh 信号传导在'关闭'和'开启'状态之间切换，以差异化调节针对 Gli 转录因子的细胞内信号级联反应。在缺乏 Hh 配体的情况下，细胞质中的 Gli 蛋白被切割形成截短型，进而转移至细胞核中并抑制靶基因的转录。Hh 与细胞表面 Patched（PTC）受体的结合稳定了 Gli 蛋白在其全长的转录激活形式上，从而刺激依赖 Hh 的基因表达（参见 Hui 和 Angers，2011 年；Briscoe 和 Therond，2013 年）。