PT  - JOURNAL ARTICLE
AU  - Danielle M Berlin
AU  - Erich J Kushner
AU  - Katy L Davis
AU  - Victoria L Bautch
TI  - Excess Centrosomes Disrupt Vascular Lumenization and Endothelial Cell Adherens Junctions
AID  - 10.1101/863787
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 863787
4099  - http://biorxiv.org/content/early/2019/12/05/863787.short
4100  - http://biorxiv.org/content/early/2019/12/05/863787.full
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.