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Abstract:
Blood flow modulates endothelial cell (EC) response
during angiogenesis. Shear stress is known to control gene expression related to the endothelialmesenchymal 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 flowderived 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.
