动脉和静脉的形成和发育需要特定类型和数量的血管内皮干细胞。我们近期的研究工作发现Hedgehog（Hh）信号是调控动脉和静脉祖细胞特化（specification）和发生的关键信号通路。Hh信号缺陷导致动脉内皮细胞缺失，而静脉内皮细胞成比例增加。动脉和静脉祖细胞如何从血管内皮干细胞分化和分离是一个重要的科学问题。本课题拟借助模式动物斑马鱼，利用CRISPR/Cas9基因敲除技术构建Hh信号通路相关基因的突变体，确定Hh 信号受体Patched对动静脉特化的直接调控作用，揭示Hh信号如何以时空方式诱导迁移中的血管内皮干细胞特化成动脉祖细胞。最后，我们还将确定Tbx20转录因子调控动静脉特化和分离的机理，并探索Tbx20是否与Hh信号协同调控动脉和静脉发育。我们的研究不仅有助于洞悉人类心脑血管疾病发生于动脉的倾向性,还将为血管自我修复的前沿疗法提供新思路。

The development of artery and vein requires specific types and numbers of endothelial stem cells. Our recent study identifies Hedgehog (Hh) signaling regulates specification and formation of arterial and venous progenitor cells. Hh signaling deficiency causes a loss of arterial progenitor cells, whereas cell numbers of venous progenitors are increased proportionally. How arterial and venous progenitor cells are differentiated and separated from endothelial stem cells is an important question. In this project, we will employ zebrafish as a model system to create Hh-signaling mutants using CRISPR/Cas9 knockdown technique, and determine whether Patched receptor regulates directly the specification of arterial and venous cells. We will explore how Hh signaling induces and converts endothelial stem cells to become arterial progenitor cells. Lastly, we will understand the mechanisms whereby Tbx20 transcriptional factor regulates the specification and separation of arteries and veins. We will also explore whether Hh signaling cooperates with Tbx20 to regulate the development of artery and vein. Our study not only provides insights into the propensity of human cardiovascular disease occurring in the arterial system, but may also aid in designing novel therapeutics for tissue self-repair.