| First Author | Bentley K | Year | 2014 |
| Journal | Nat Cell Biol | Volume | 16 |
| Issue | 4 | Pages | 309-21 |
| PubMed ID | 24658686 | Mgi Jnum | J:218866 |
| Mgi Id | MGI:5618599 | Doi | 10.1038/ncb2926 |
| Citation | Bentley K, et al. (2014) The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis. Nat Cell Biol 16(4):309-21 |
| abstractText | 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. |
