弓动脉是脊椎动物胚胎发育时期连接心脏和背主动脉的血管，其发育稳态缺陷与先天性心血管疾病密切相关。然而，关于弓动脉细胞的起源、弓动脉血管的形成及分子调控机制等重要的科学问题存在着大量争论。在本项目前期研究工作中，我们利用斑马鱼在活体胚胎成像方面的优势，通过在活体胚胎中的细胞谱系观测和追踪，初步发现心区侧板中胚层细胞迁移至咽区形成细胞索；咽区细胞索“出芽”，形成弓动脉原基；弓动脉原基进一步增殖、迁移、分化，形成弓动脉。更为重要的是，来自内胚层的咽囊对于弓动脉原基的发育具有不可替代的重要作用。本项目将充分利用我们独具特色的研究平台，结合体内体外的功能研究，对咽囊通过表达并分泌关键信号分子，激活下游信号通路，调控弓动脉原基发生、增殖、迁移和分化的分子机制进行系统深入的研究，不仅将在弓动脉发育稳态的分子调控网络方面取得原始创新性的重要进展，还将为理解相关疾病发生发展的分子机理提供坚实的基础。

Aortic arch arteries are symmetrical pairs of blood vessels connecting the heart with dorsal aortae during vertebrate embryonic development. Aberrant PAA developmental homeostasis results in vascular defects frequently observed in patients with lethal congenital heart diseases. However, there are a great deal of disputes regarding the developmental process of aortic arch arteries. Taking the advantage of the live embryo imaging during zebrafish development, cell lineage tracing experiments were performed in the preliminary work of the current project. We find that endothelial progenitors in the heart field migrate toward the pharyngeal region and assemble into a cell cord. Then some endothelial progenitors successively migrate out of the pharyngeal cell cord and develop into several aortic arch artery buds. These buds ultimately bloom into functional aortic arch arteries through cell proliferation, migration and differentiation processes. Importantly, our data also reveal that the pharyngeal pouches, which form by budding of the foregut endoderm, are essential for the morphogenesis of aortic arch arteries. Using our unique research platform, we will focused on the functional mechanism of pharyngeal pouches in regulating cell proliferation, migration and differentiation during aortic arch artery development. Our study will identify the origin of endothelial progenitors giving rise to the aortic arch arteries and elucidate the molecular mechanisms of pharyngeal pouch-mediated regulation of developmental homeostasis during aortic arch artery formation, which is important for understanding of the related congenital heart diseases.