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VE‐cadherin and avb3 integrin‐mediated collective cell migration and patterning during vasculogenesis
Author(s) -
Czirok Andras,
Perryn Erica D,
Szabo Andras,
Little Charles D
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a35-a
Subject(s) - vasculogenesis , integrin , microbiology and biotechnology , motility , chemotaxis , biology , ve cadherin , angiogenesis , sprouting angiogenesis , live cell imaging , cadherin , cell , neovascularization , receptor , cancer research , stem cell , biochemistry , progenitor cell , genetics
Primary vascular plexus patterning, before the onset of circulation, is a collective action of primordial endothelial cells. To understand the patterning mechanism, we combined time‐lapse imaging of avian embryos and mouse allantoic explants with computer modeling. Endothelial cells were visualized through fluorescence‐labeled antibodies in time‐lapse recordings lasting up to 24hrs. Integrin, VEGF and VE cadherin function was perturbed by monoclonal antibodies. Cell‐autonomous motility and tissue motion was calculated from the image sequences. Our data revealed that primary vascular plexus formation involves the elongation of vasculogenic sprouts. Utilizing avb3 integrins, these multicellular sprouts invade rapidly into avascular areas, eventually creating a polygonal pattern. Sprout elongation, in turn, depends on a continuous supply of endothelial cells, streaming along the sprout towards its tip. Blocking VE cadherin function can substantially reduce the endothelial cell streaming behavior. To demonstrate that cell‐cell contact interactions are sufficient to produce polygonal patterns, we formulated and analyzed a simple mathematical model. The model exhibits robust sprouting dynamics and results in patterns with morphometry similar native primordial vascular plexuses — without ancillary assumptions involving chemotaxis or chemomechanical signaling. The results show that vasculogenic sprouts are of central importance in controlling the geometry of the primordial vascular network, representing an important target for neovascularization strategies, and tissue engineering. Support: American Heart Association 0535245N, 0410084Z; NIH HL068855 and the Mathers Charitable Foundation.