Vascular sprout formation entails tissue deformations and VE-cadherin-dependent cell-autonomous motility.
Embryonic and fetal vascular sprouts form within constantly expanding tissues. Nevertheless, most biological assays of vascular spouting are conducted in a static mechanical milieu. Here we study embryonic mouse allantoides, which normally give raise to an umbilical artery and vein. However, when placed in culture, allantoides assemble a primary vascular network. Unlike other in vitro assays, allantoic primordial vascular cells are situated on the upper surface of a cellular layer that is engaged in robust spreading motion. Time-lapse imaging allows quantification of primordial vascular cell motility as well as the underlying mesothelial tissue motion. Specifically, we calculate endothelial cell-autonomous motion by subtracting the tissue-level mesothelial motion from the total endothelial cell displacements. Formation of new vascular polygons is hindered by administration of function-blocking VE-cadherin antibodies. Time-lapse recordings reveal that (1) cells at the base of sprouts normally move distally "over" existing sprout cells to form new tip-cells; and (2) loss of VE-cadherin activity prevents this motile behavior. Thus, endothelial cell-cell-adhesion-based motility is required for the advancement of vascular sprouts within a moving tissue environment. To the best of our knowledge, this is the first study that couples endogenous tissue dynamics to assembly of vascular networks in a mammalian system.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Erica D
ED
Perryn
András
A
Czirók
Charles D
CD
Little
D000482:Allantois / Q000098:blood supply; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D003470:Culture Media; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000939:Epitopes; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018715:Microscopy, Video; D009024:Morphogenesis; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009924:Organ Culture Techniques; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D000099152:Cadherin 5
D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D015820:Cadherins; D003470:Culture Media; D000939:Epitopes; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099152:Cadherin 5; C485182:Cyan Fluorescent Protein