Differential regulation of angiogenesis and blood-brain barrier formation in zebrafish

血脑屏障（BBB）是由神经血管单位建立的通透性屏障，以确保脑组织稳态，防止有毒物质或病原体进入中枢神经系统。在脑血管形成和血脑屏障形成的不同步骤中，Wnt信号是活跃和必需的。我们发现了一种新的Wnt信号在脑血管生成过程中的调节功能，以及一种新的Wnt和S1P信号通路的串扰。因此，我们旨在了解Wnt和S1P信号在脑毛细血管生成、血脑屏障形成和维持中的具体作用，特别是两种途径在机制水平上的相互作用。在这项工作中，我们将利用斑马鱼作为模式生物的优势，特别是它易于活成像和快速转基因和基因组编辑，并结合使用原代分离的小鼠脑内皮细胞作为发育中的血管生成活性脑毛细血管的模型。我们期望对Wnt和S1P信号之间的串扰如何调节血脑屏障的发育和维持获得新的见解。

The blood-brain barrier (BBB) is a permeability barrier established by the neurovascular unit to ensure brain tissue homeostasis and prevent toxic substances or pathogens from entering the central nervous system.Wnt signaling is active and required during different steps of brain vascularization and BBB formation. We have identified a novel regulatory function of Wnt signaling during brain angiogenesis and a novel crosstalk of the Wnt and Sphingosine 1 phosphate (S1P) signaling pathways. We therefore aim to understand the specific contributions of Wnt and S1P signaling to brain capillary angiogenesis, BBB formation and maintenance and especially the interaction of both pathways on a mechanistic level. For this work, we will exploit the advantages of the zebrafish as a model organism, especially its amenability to live imaging and fast transgenesis and genome editing in combination with using primary isolated mouse brain endothelial cells as a model for the developmental angiogenically active brain capillaries. We expect to gain novel insights into how the crosstalk between Wnt and S1P signaling regulates development and maintenance of the BBB.