Zhang Yu, Xu Bing, Chen Qi, Yan Yong, Du Jiulin, Du Xufei
Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
School of Future Technology, University of Chinese Academy of Sciences, Beijing, China.
Front Mol Neurosci. 2018 Jun 28;11:222. doi: 10.3389/fnmol.2018.00222. eCollection 2018.
During development, immature blood vessel networks remodel to form a simplified and efficient vasculature to meet the demand for oxygen and nutrients, and this remodeling process is mainly achieved via the pruning of existing vessels. It has already known that the migration of vascular endothelial cells (ECs) is one of the mechanisms underlying vessel pruning. However, the role of EC apoptosis in vessel pruning remains under debate, especially in the brain. Here, we reported that EC apoptosis makes a significant contribution to vessel pruning in the brain of larval zebrafish. Using long-term time-lapse confocal imaging of the brain vasculature in zebrafish larvae, we found that EC apoptosis was always accompanied with brain vessel pruning and about 15% of vessel pruning events were resulted from EC apoptosis. In comparison with brain vessels undergoing EC migration-associated pruning, EC apoptosis-accompanied pruned vessels were longer and showed higher probability that the nuclei of neighboring vessels' ECs occupied their both ends. Furthermore, we found that microglia were responsible for the clearance of apoptotic ECs accompanying vessel pruning, though microglia themselves were dispensable for the occurrence of vessel pruning. Thus, our study demonstrates that EC apoptosis contributes to vessel pruning in the brain during development in a microglial cell-independent manner.
在发育过程中，不成熟的血管网络会进行重塑，以形成一个简化且高效的脉管系统，以满足对氧气和营养物质的需求，而这种重塑过程主要是通过对现有血管的修剪来实现的。已知血管内皮细胞（ECs）的迁移是血管修剪的潜在机制之一。然而，EC凋亡在血管修剪中的作用仍存在争议，尤其是在大脑中。在此，我们报告EC凋亡对斑马鱼幼体大脑中的血管修剪有显著贡献。通过对斑马鱼幼体脑血管进行长期延时共聚焦成像，我们发现EC凋亡总是伴随着脑血管修剪，并且约15%的血管修剪事件是由EC凋亡导致的。与经历与EC迁移相关修剪的脑血管相比，伴随EC凋亡而修剪的血管更长，并且相邻血管EC的细胞核占据其两端的概率更高。此外，我们发现小胶质细胞负责清除伴随血管修剪的凋亡EC，尽管小胶质细胞本身对于血管修剪的发生并非必需。因此，我们的研究表明，EC凋亡以一种不依赖小胶质细胞的方式，在发育过程中对大脑中的血管修剪有贡献。
