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| 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 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 4 |
| Page Range: | 309-321 |
| Date: | April 2014 |
| Official Publication: | https://doi.org/10.1038/ncb2926 |
| PubMed: | View item in PubMed |
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