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

Bentley, Katie, Franco, Claudio Areias, Philippides, Andrew, Blanco, Raquel, Dierkes, Martina, Gebala, Véronique, Stanchi, Fabio, Jones, Martin, Aspalter, Irene M, Cagna, Guiseppe, Weström, Simone, Claesson-Welsh, Lena, Vestweber, Dietmar and Gerhardt, Holger (2014) The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis. Nature Cell Biology, 16 (4). pp. 309-321. ISSN 1465-7392

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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.

Item Type: Article
Schools and Departments: School of Engineering and Informatics > Informatics
Research Centres and Groups: Centre for Computational Neuroscience and Robotics
Sussex Neuroscience
Depositing User: Thomas Nowotny
Date Deposited: 21 Jun 2019 10:23
Last Modified: 08 Mar 2021 16:15

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