再生早期启动信号的发现及功能解析对于再生机制研究至关重要。目前对再生起始信号的研究集中在斑马鱼等低等物种，在羊膜动物中研究较少。多疣壁虎断尾再生是研究羊膜动物再生机制的理想模型。本课题组经单细胞转录组研究发现：损伤导致施万细胞去分化并高表达形态发生素Sonic Hedgehog（SHH），阻断SHH通路显著抑制再生，表明SHH是一个起始再生的关键分子，因此本课题拟对其在再生中的效应和机制进行研究：探讨再生组织中SHH、施万细胞及轴突的时空分布特征，论证去分化施万细胞来源的SHH是否介导神经支配影响再生的效应；在体内外模型中研究SHH信号对再生的效应及与神经元来源因子间的协同作用；结合多组织的单细胞转录组数据对SHH及相关通路的配受体分析，通过体内外功能研究阐明SHH信号的分子机制；并进一步研究SHH信号分子被损伤中何种因素激活。本课题为理解不同物种器官和组织再生机制的演化过程增加了新内容。

The identification and functional study of initial signals is the key issue to understand mechanism of regeneration. The signal pathway for regeneration initiation is mainly focused on the lower species such as zebra fish, while is still elusive in amniotes. Gekko japonicus is a feasible regeneration model for amniotes. Our previous data of single-cell RNA- Seq revealed that Schwann cells undergoing de-differentiation expressed morphogen Sonic Hedgehog（SHH）upon injury, and SHH blockade resulted in inhibition of tail regeneration. Therefore, we aim to investigate the effects and mechanism of SHH signals on tail regeneration. First, we will define the spatial distribution of SHH signal, Schwann cells and axon in regenerated tissues, and investigate whether and how SHH mediates effects of innervation on regeneration. Thereafter, we will perform the study for the effect of SHH signal on tail regeneration with both in vivo and in vitro model. In further, we will investigate whether the factors from neuron could affect the regeneration together with SHH signal. Then, we will analyze the expression profile of ligands and receptors for SHH and related signal pathway according single-cell transcriptome data, predict the possible cross-cellular interaction, and decipher the mechanism of SHH mediated effects with the functional assay. Finally, we will answer what signal triggers the expression of SHH in Schwann cells upon injury. This study will be useful to understand the evolution of molecular mechanism of organ or tissue regeneration in gecko and other species.