How Vascular Networks Form - in Fish Brains
Though the human brain comprises only 2 percent of body weight it receives up to 15 percent of the cardiac output through a network of vessel vasculature
How the intricate network of blood vessels forms within the brain has long fascinated biologists. The vasculature in the human brain consists of a complex branching network of blood vessels, in total some several hundred miles in length.
The network is formed to distribute blood efficiently to all brain regions, and abnormalities can lead to various neurological disorders, including strokes, learning difficulties and neurodegeneration. Yet our knowledge of just how the brain vasculature develops remains relatively limited.
In this study, published August 14 in the open access journal PLOS Biology, Dr. Jiu-lin Du's research group at the Institute of Neuroscience, the Chinese Academy of Sciences, employed zebrafish as a simple vertebrate animal model and adopted a multi-disciplinary approach.
They revealed that the 'vessel pruning' that naturally takes place during development (where the vasculature system develops its optimum, relatively simplified final form by forcing the disappearance of some vessels) is driven by brain blood flowvia the lateral migration of cells that make up the vessels.
Using high resolution microscopy that allows reconstruction of tridimensional images, the researchers analyzed larval zebrafish during the course of development to examine the exact nature of the pruning.
It was found that in early development
the vasculature in the fish consisted of many loops,
and that during early developmentpruning tends
to occur at these loop-forming segments.
Some 45 percent of early-formed vessel segments
were pruned during brain development.
Comparing pruned and unpruned blood vessels, it was apparent that blood flow decreased in vessels prior to the onset of pruning, and when the researchers artificially blocked blood flow in specific vessels this led to vessel pruningwhereas increasing blood flow inhibited pruning in the vessels concerned.
In investigating the molecular mechanisms
that regulate this process, scientists found
that vessel pruning was mainly mediated
by the expression of Rac1,
a protein known to drive migration
of the cells concerned.
This study in fish brain development provides new insight into how vessel segments are pruned in the development of the brain's network of blood vessels. The researchers trust it will spark more investigation into vascular research, offering further potential for understanding the importance of the vasculature system in cancer maintenance and metastasis.
Funding: This work was supported by grants from the National Basic Research Program of China (2012CB945101, 2011CBA00400 and 2006CB943800), Shanghai government (06dj14010, 07pj14107) and the Hundred Talents Program from Chinese Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Citation: Chen Q, Jiang L, Li C, Hu D, Bu J-w, et al. (2012) Haemodynamics-Driven Developmental Pruning of Brain Vasculature in Zebrafish. PLoS Biol 10(8): e1001374. doi:10.1371/journal.pbio.1001374
Original article: http://www.eurekalert.org/pub_releases/2012-08/plos-nii080812.php