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Front Mol Neurosci. 2018 Jun 28;11:222. doi: 10.3389/fnmol.2018.00222. eCollection 2018.

Apoptosis of Endothelial Cells Contributes to Brain Vessel Pruning of Zebrafish During Development.

Zhang Y1,2, Xu B1,2, Chen Q1, Yan Y1,3, Du J1,2,3, Du X1,2.

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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.
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.


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 in vivo 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.


apoptosis; endothelial cells; microglia; vessel pruning; zebrafish

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