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The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis

Item Type:Article
Title:The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis
Creators Name:Bentley, K., Franco, C.A., Philippides, A., Blanco, R., Dierkes, M., Gebala, V., Stanchi, F., Jones, M., Aspalter, I.M., Cagna, G., Weström, S., Claesson-Welsh, L., Vestweber, D. and Gerhardt, H.
Abstract:Endothelial cells show surprising cell rearrangement behaviour during angiogenic sprouting; however, the underlying mechanisms and functional importance remain unclear. By combining computational modelling with experimentation, we identify that Notch/VEGFR-regulated differential dynamics of VE-cadherin junctions drive functional endothelial cell rearrangements during sprouting. We propose that continual flux in Notch signalling levels in individual cells results in differential VE-cadherin turnover and junctional-cortex protrusions, which powers differential cell movement. In cultured endothelial cells, Notch signalling quantitatively reduced junctional VE-cadherin mobility. In simulations, only differential adhesion dynamics generated long-range position changes, required for tip cell competition and stalk cell intercalation. Simulation and quantitative image analysis on VE-cadherin junctional patterning in vivo identified that differential VE-cadherin mobility is lost under pathological high VEGF conditions, in retinopathy and tumour vessels. Our results provide a mechanistic concept for how cells rearrange during normal sprouting and how rearrangement switches to generate abnormal vessels in pathologies.
Keywords:Cadherins, CD Antigens, Cell Adhesion, Cell Movement, Computer-Assisted Image Processing, Computer Simulation, Cultured Cells, Diabetic Retinopathy, Endothelial Cells, Intercellular Junctions, Notch Receptors, Pathologic Neovascularization, Signal Transduction, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2, Animals, Mice
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:309-321
Date:April 2014
Official Publication:https://doi.org/10.1038/ncb2926
PubMed:View item in PubMed

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