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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-03-23

AUTHORS

Katie Bentley, Claudio Areias Franco, Andrew Philippides, Raquel Blanco, Martina Dierkes, Véronique Gebala, Fabio Stanchi, Martin Jones, Irene M. Aspalter, Guiseppe Cagna, Simone Weström, Lena Claesson-Welsh, Dietmar Vestweber, Holger Gerhardt

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. More... »

PAGES

309-321

References to SciGraph publications

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  • 2013-04-09. VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation in NATURE COMMUNICATIONS
  • 2007-01-28. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis in NATURE
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  • 2006-10-22. VEGF controls endothelial-cell permeability by promoting the β-arrestin-dependent endocytosis of VE-cadherin in NATURE CELL BIOLOGY
  • 2010-09-26. Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting in NATURE CELL BIOLOGY
  • 2009-07-16. Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window in NATURE PROTOCOLS
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  • Journal

    TITLE

    Nature Cell Biology

    ISSUE

    4

    VOLUME

    16

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncb2926

    DOI

    http://dx.doi.org/10.1038/ncb2926

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1000429118

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24658686


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    363 grid-institutes:grid.5596.f schema:alternateName Department of Oncology, Vascular Patterning Laboratory, VIB3-Vesalius Research Center & CMVB, KU Leuven Campus Gasthuisberg O&N4, Herestraat 49 box 912 B-3000 Leuven, Belgium
    364 schema:name Department of Oncology, Vascular Patterning Laboratory, VIB3-Vesalius Research Center & CMVB, KU Leuven Campus Gasthuisberg O&N4, Herestraat 49 box 912 B-3000 Leuven, Belgium
    365 Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY, UK
    366 rdf:type schema:Organization
    367 grid-institutes:grid.8993.b schema:alternateName Department of Immunology, Uppsala University, Genetics and Pathology, Rudbeck Laboratory, Dag Hammarskjöldsv. 20 751 85 Uppsala, Sweden
    368 schema:name Department of Immunology, Uppsala University, Genetics and Pathology, Rudbeck Laboratory, Dag Hammarskjöldsv. 20 751 85 Uppsala, Sweden
    369 rdf:type schema:Organization
     




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