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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. and Franco, C.A. and Philippides, A. and Blanco, R. and Dierkes, M. and Gebala, V. and Stanchi, F. and Jones, M. and Aspalter, I.M. and Cagna, G. and Weström, S. and Claesson-Welsh, L. and 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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