Angiogenic sprouting needs to be tightly controlled. It has been suggested that the Notch ligand dll4 expressed in leading tip cells restricts angiogenesis by activating Notch signalling in trailing stalk cells. Here, we show using live imaging in zebrafish that activation of Notch signalling is rather required in tip cells. Notch activation initially triggers expression of the chemokine receptor cxcr4a. This allows for proper tip cell migration and connection to the pre-existing arterial circulation, ultimately establishing functional arterial-venous blood flow patterns. Subsequently, Notch signalling reduces cxcr4a expression, thereby preventing excessive blood vessel growth. Finally, we find that Notch signalling is dispensable for limiting blood vessel growth during venous plexus formation that does not generate arteries. Together, these findings link the role of Notch signalling in limiting angiogenesis to its role during artery formation and provide a framework for our understanding of the mechanisms underlying blood vessel network expansion and maturation.

中文翻译：

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内皮Notch信号通过控制动脉形成来限制血管生成。


需要严格控制血管生成萌芽。有人提出，前导尖端细胞中表达的Notch配体dll4通过激活尾随茎细胞中的Notch信号传导来限制血管生成。在这里，我们使用斑马鱼的实时成像表明，尖端细胞相当需要Notch信号的激活。 Notch 激活首先触发趋化因子受体 cxcr4a 的表达。这允许适当的尖端细胞迁移并连接到预先存在的动脉循环，最终建立功能性动静脉血流模式。随后，Notch 信号传导会降低 cxcr4a 的表达，从而防止血管过度生长。最后，我们发现Notch信号传导对于限制不生成动脉的静脉丛形成期间的血管生长是可有可无的。总之，这些发现将 Notch 信号传导在限制血管生成中的作用与其在动脉形成过程中的作用联系起来，并为我们理解血管网络扩张和成熟的机制提供了一个框架。