Vascular sprout formation entails tissue deformations and VE-cadherin-dependent cell-autonomous motility

Dev Biol. 2008 Jan 15;313(2):545-55. doi: 10.1016/j.ydbio.2007.10.036. Epub 2007 Nov 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allantois / blood supply
  • Animals
  • Antigens, CD / metabolism*
  • Antigens, CD34 / metabolism
  • Biomarkers / metabolism
  • Cadherins / metabolism*
  • Cell Adhesion
  • Cell Movement / physiology*
  • Culture Media
  • Endothelial Cells / physiology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / embryology
  • Endothelium, Vascular / metabolism
  • Epitopes
  • Female
  • Fluorescent Dyes / metabolism
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Inbred Strains
  • Microscopy, Video
  • Morphogenesis
  • Neovascularization, Physiologic / physiology*
  • Organ Culture Techniques
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Pregnancy


  • Antigens, CD
  • Antigens, CD34
  • Biomarkers
  • Cadherins
  • Culture Media
  • Cyan Fluorescent Protein
  • Epitopes
  • Fluorescent Dyes
  • Platelet Endothelial Cell Adhesion Molecule-1
  • cadherin 5
  • Green Fluorescent Proteins