On Aug 14, 2012, Dr. Jiu-lin Dua€？s research group at the Institute of Neuroscience, Chinese Academy of Sciences, published a research article entitled "Haemodynamics-Driven Developmental Pruning of Brain Vasculature in Zebrafish" in PLoS BIOLOGY. This work was also highlighted by SYNOPSES in the current issue of the journal.

　　How the brain vascular network forms during development has long been fascinating biologists. The brain comprises only 2% of body weight but receives up to about 15% of cardiac output through its blood vasculature. The brain vasculature consists of a highly ramified vessel network with a total vessel length of a few hundred miles in the human and is tailored for efficiently distributing the blood to all brain regions. Abnormalities of the brain vasculature can lead to neurological disorders, including stroke, mental retardation, and neurodegeneration. However, our knowledge about brain vascular development is quite limited.

　　In this study, by using zebrafish as a simple vertebrate animal model and multi-disciplinary approaches, the authors reveal that changes of brain blood flow drive vessel pruning via lateral migration of vascular endothelial cells (ECs), leading to the simplification of the brain vascular network and efficient routing of blood flow in the developing brain.

　　The authors first performed in vivo long-term time-lapse imaging of whole-midbrain vasculature in zebrafish larvae from 1.5 to 7.5 days post-fertilization and captured the developmental process of the 3-D midbrain vasculature. They developed a sophisticated method to systematically analyze both the morphological and topological properties of the brain vasculature. Counterintuitively, the authors found that, accompanying its developmental expansion, the 3-D brain vasculature is remodeled from an initially exuberant interconnected meshwork into a simplified architecture that facilitates efficient arteriovenous blood flow. By tracing the fate of each vessel segment, they demonstrated that this structure simplification is due to selective vessel pruning of early-formed and loop-constituting vessel segments. They then simultaneously monitored changes in both the morphology and blood flow of vessel segments during the pruning process, and found that pruned segments exhibit low and variable blood flow, which further decreases irreversibly before the initiation of pruning. Combining local manipulation of brain blood flow and fluid dynamics-based simulation of realistic 3-D brain vasculature, the authors demonstrated that the vessel pruning is driven by blood flow changes. At cellular and molecular levels, vessel pruning was found to be mainly mediated by Rac1-involved migration of ECs from pruned to unpruned segments rather than EC apoptosis, an efficient way for reconstructing the brain vasculature.

　　This study reveals an essential role of vessel pruning in brain vascular development and provides a novel insight into how vessel segments are pruned. It will spark further investigation in the vascular research field. Considering the importance of the vasculature system in cancer maintenance and metastasis, understanding vessel pruning may offer a new strategy for cancer therapy.

　　This work was carried out by graduate student Qi Chen, post-doctoral fellow Luan Jiang, and technicians Chun Li and Jiwen Bu, under the supervision of Dr. Jiu-lin Du, in collaboration with Drs. David Cai and Dan Hu in Department of Mathematics and Institute of Natural Sciences, Shanghai Jiaotong University, and supported by the grants from Ministry of Science and Technology of China, Chinese Academy of Sciences, Shanghai Municipal Government, and State Key Laboratory of Neuroscience.

　　Figure a shows the brain tissue (red) and blood vasculature (green). 

　　Figure b shows vessel pruning (red arrow) and angiogenesis (white arrowhead) in the developing brain vasculature.

　　Figure c depicts that EC migration-associated vessel pruning simplifies brain vascular network and facilitates blood flow.