RT Journal Article
SR Electronic
T1 Excess Centrosomes Disrupt Vascular Lumenization and Endothelial Cell Adherens Junctions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 863787
DO 10.1101/863787
A1 Danielle M Berlin
A1 Erich J Kushner
A1 Katy L Davis
A1 Victoria L Bautch
YR 2019
UL http://biorxiv.org/content/early/2019/12/05/863787.abstract
AB Proper blood vessel formation requires coordinated changes in endothelial cell polarity and rearrangement of cell-cell junctions to form a functional lumen. One important regulator of cell polarity is the centrosome, which acts as a microtubule organizing center. Excess centrosomes perturb aspects of endothelial cell polarity linked to migration, but whether centrosome number influences apical-basal polarity and cell-cell junctions is unknown. Here, we show that excess centrosomes alter the apical-basal polarity of endothelial cells in angiogenic sprouts and disrupt endothelial cell-cell adherens junctions. Endothelial cells with excess centrosomes had narrower lumens in a 3D sprouting angiogenesis model, and zebrafish intersegmental vessels had reduced perfusion following centrosome overduplication. These results indicate that endothelial cell centrosome number regulates proper lumenization downstream of effects on apical-basal polarity and cell-cell junctions. Endothelial cells with excess centrosomes are prevalent in tumor vessels, suggesting how centrosomes contribute to the dysfunction of tumor vasculature.