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The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis
journal contribution
posted on 2023-06-09, 18:08 authored by Katie Bentley, Claudio Areias Franco, Andy PhilippidesAndy Philippides, Raquel Blanco, Martina Dierkes, Véronique Gebala, Fabio Stanchi, Martin Jones, Irene M Aspalter, Guiseppe Cagna, Simone Weström, Lena Claesson-Welsh, Dietmar Vestweber, Holger GerhardtEndothelial 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.
History
Publication status
- Published
File Version
- Published version
Journal
Nature Cell BiologyISSN
1465-7392Publisher
Nature ResearchExternal DOI
Issue
4Volume
16Page range
309-321Department affiliated with
- Informatics Publications
Research groups affiliated with
- Centre for Computational Neuroscience and Robotics Publications
- Sussex Neuroscience Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2019-06-21First Compliant Deposit (FCD) Date
2021-03-08Usage metrics
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