Unravelling the role of aquaporins in blood vessel development

1.aqp1a.1、aqp8a.1和/或aqp1a.1基因敲除导致斑马鱼躯干节间血管形成不完全。这种表型是由于水通道蛋白突变体中有缺陷的出芽血管生成所致。在血管萌发过程中，aqp1a.1在背主动脉表达，而aqp8a.1不表达，aqp1a.1在顶端细胞和可能从背主动脉突起的内皮细胞中表达丰富。在缺乏aqp1a.1和aqp8a.1的情况下，在ISV形成期间，内皮细胞从背主动脉伸出的时间延迟，末端细胞的速度减慢。此外，Aqp1a.1和Aqp8a.1的丢失导致形成的丝状伪足的数量减少，丝状伪足长度减少。在没有丝状孔道的情况下，野生型内皮细胞仍然能够迁移形成ISV，而水通道蛋白突变体中的内皮细胞则不能，这表明在萌发血管形成过程中，丝状通道介导的迁移和水通道蛋白可能共同发挥作用，促进EC迁移。我们还发现，aqp1a.1的缺失而不是aqp8a.1的缺失会导致造血干细胞和祖细胞(HSPC)形成的减少。在斑马鱼中，HSPC是通过背主动脉腹底的血源性内皮细胞萌发而产生的。

1. Knockout of aqp1a.1, aqp8a.1 or both genes results in incomplete formation of intersegmental vessels (ISVs) in the zebrafish trunk. This phenotype is due to a defective sprouting angiogenesis in aquaporin mutants.2. During sprouting angiogenesis aqp1a.1 but not aqp8a.1 is expressed in the dorsal aorta, and aqp1a.1 expression is enriched in tip cells and in endothelial cells (ECs) that would be protrude from the dorsal aorta.3. In the absence of aqp1a.1 and aqp8a.1 there is a delay in endothelial tip cell protrusion from the dorsal aorta and a decrease in tip cell velocity during ISV formation. Also, the loss of both Aqp1a.1 and Aqp8a.1 led to a decrease in the number of the formed filopodia as well as a decrease in filopodia length. In the absence of filopodia, wild type ECs are still able to migrate to form ISVs, while ECs in aquaporin mutants are not, suggesting that both filopodia-mediated migration and aquaporins may function synergistically to promote EC migration during sprouting angiogenesis.4. We also found that the loss of aqp1a.1 but not aqp8a.1 results in a decrease of hematopoietic stem and progenitor cells (HSPCs) formation. In the zebrafish, HSPCs are generated through the budding of hemogenic ECs from the ventral floor of the dorsal aorta.