Final Report Summary - ZEBRAFISHANGIO (Analysis of flow regulated angiogenesis during zebrafish development)
Our analysis on the influence of blood flow on vascular patterning revealed that the removal of unwanted blood vessel connections during development, also referred to as pruning of blood vessels or regression, was greatly influenced by changes in hemodynamics. We investigated the pruning of the ocular vasculature and for the first time showed the cellular dynamics during this process. Our imaging approach revealed that initially multicellular blood vessels rearrange to form a unicellular tube before regression. We hypothesize that this rearrangement reduces the likelihood of vascular leakage. We furthermore show that differences in blood flow between neighboring vessels can induce blood vessel pruning, while an absence of blood flow per se does not induce this behavior in blood vessels. Together, our studies elucidate several key morphogenetic principles during blood vessel development and regression that are shared between embryonic and regenerative processes and identified the chemokine receptor cxcr4a as an important player in regulating endothelial cell migratory behaviors. Additionally, we established technological advances concerning long-term anesthesia that will facilitate the imaging of regenerative processes in adult zebrafish.