Primary cilia are immotile appendages that have evolved to receive and interpret a variety of different extracellular cues. Cilia play crucial roles in intercellular communication during development and defects in cilia affect multiple tissues accounting for a heterogeneous group of human diseases called ciliopathies. The Hedgehog (Hh) signaling pathway is one of these cues and displays a unique and symbiotic relationship with cilia. Not only does Hh signaling require cilia for its function but the majority of the Hh signaling machinery is physically located within the cilium-centrosome complex. More specifically, cilia are required for both repressing and activating Hh signaling by modifying bifunctional Gli transcription factors into repressors or activators. Defects in balancing, interpreting or establishing these repressor/activator gradients in Hh signaling either require cilia or phenocopy disruption of cilia. Here, we will summarize the current knowledge on how spatiotemporal control of the molecular machinery of the cilium allows for a tight control of basal repression and activation states of the Hh pathway. We will then discuss several paradigms on how cilia influence Hh pathway activity in tissue morphogenesis during development. Last, we will touch on how cilia and Hh signaling are being reactivated and repurposed during adult tissue regeneration. More specifically, we will focus on mesenchymal stem cells within the connective tissue and discuss the similarities and differences of how cilia and ciliary Hh signaling control the formation of fibrotic scar and adipose tissue during fatty fibrosis of several tissues.

初级纤毛是不动的附属物，已进化为接收和解释各种不同的细胞外信号。纤毛在发育过程中的细胞间通讯中发挥着至关重要的作用，纤毛缺陷会影响多个组织，从而导致称为纤毛病的一组异质性人类疾病。 Hedgehog (Hh) 信号通路是这些线索之一，并与纤毛表现出独特的共生关系。 Hh 信号传导不仅需要纤毛才能发挥其功能，而且大部分 Hh 信号传导机制物理上位于纤毛-中心体复合体内。更具体地说，纤毛通过将双功能 Gli 转录因子修饰为阻遏物或激活物来抑制和激活 Hh 信号传导。 Hh 信号传导中平衡、解释或建立这些阻遏物/激活物梯度的缺陷要么需要纤毛，要么需要纤毛的表型破坏。在这里，我们将总结关于纤毛分子机制的时空控制如何严格控制 Hh 通路的基础抑制和激活状态的当前知识。然后我们将讨论纤毛如何影响发育过程中组织形态发生中 Hh 通路活性的几种范例。最后，我们将讨论纤毛和 Hh 信号在成体组织再生过程中如何被重新激活和重新利用。更具体地说，我们将重点关注结缔组织内的间充质干细胞，并讨论纤毛和纤毛 Hh 信号在多种组织脂肪纤维化过程中如何控制纤维化疤痕和脂肪组织形成的异同。