Blood Flow Limits Endothelial Cell Extrusion in the Zebrafish Dorsal Aorta.

Blood flow modulates endothelial cell (EC) response during angiogenesis. Shear stress is known to control gene expression related to the endothelial-mesenchymal transition and endothelial-hematopoietic transition. However, the impact of blood flow on the cellular processes associated with EC extrusion is less well understood. To address this question, we dynamically record EC movements and use 3D quantitative methods to segregate the contributions of various cellular processes to the cellular trajectories in the zebrafish dorsal aorta. We find that ECs spread toward the cell extrusion area following the tissue deformation direction dictated by flow-derived mechanical forces. Cell extrusion increases when blood flow is impaired. Similarly, the mechanosensor polycystic kidney disease 2 (pkd2) limits cell extrusion, suggesting that ECs actively sense mechanical forces in the process. These findings identify pkd2 and flow as critical regulators of EC extrusion and suggest that mechanical forces coordinate this process by maintaining ECs within the endothelium.