The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis
2014 (English)In: Nature Cell Biology, ISSN 1465-7392, Vol. 16, no 4, 309-321 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2014. Vol. 16, no 4, 309-321 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-224347DOI: 10.1038/ncb2926ISI: 000333556900005OAI: oai:DiVA.org:uu-224347DiVA: diva2:716998