Expanding roles for alpha 4 integrin and its ligands in development

Cell Adhes Commun. 1994 Apr;2(1):27-43. doi: 10.3109/15419069409014200.


Interaction of alpha 4 integrins with vascular cell adhesion molecule-1 (VCAM-1) is classically important for immune function. However, we found recently that these receptors have a second role, in embryogenesis, where they mediate cell-cell interactions that are important for skeletal muscle differentiation. Here, we present evidence of an expanding role for these receptors in murine development. alpha 4 and VCAM-1 were found at embryonic sites of hematopoiesis, suggesting a role for these receptors during embryogenesis that parallels their hematopoietic function in adult bone marrow. During angiogenesis in the lung, alpha 4 and VCAM-1 were found on mesenchyme that gives rise to vascular endothelium and smooth muscle. alpha 4 persisted on the smooth muscle and the endothelium of newly forming vessels where it colocalized with its extracellular matrix ligand, fibronectin (FN). These patterns suggest several roles for alpha 4 integrins and their ligands in angiogenesis. alpha 4 was also found on neural crest derivatives where it colocalized with FN. alpha 4 was expressed selectively on cells in the dorsal root ganglia: it was apparent along ventral projections, but absent from dorsal projections, suggesting that alpha 4 integrins could be involved in defining neuronal fates. Although VCAM-1 was not expressed on most neural crest derivatives, it was found in the neural crest-derived outflow tract of the embryonic heart, where it colocalized with alpha 4. These results imply that alpha 4 integrins and their ligands could be important for migration or differentiation of neural crest. alpha 4 was also expressed on embryonic retina and FN was found on inductive mesenchyme surrounding the eye, suggesting a role for these proteins in eye development. Finally, based on their patterns of expression, we conclude that VCAM-1 only participates in a subset of interactions involving alpha 4 integrins, whereas FN appears to be the more general ligand.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology*
  • Animals
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / physiology*
  • Embryonic and Fetal Development*
  • Endothelium, Vascular / embryology
  • Endothelium, Vascular / growth & development
  • Endothelium, Vascular / metabolism*
  • Female
  • Fibronectins / analysis
  • Fibronectins / biosynthesis
  • Fibronectins / physiology*
  • Gene Expression
  • Heart / embryology
  • Heart / growth & development
  • Integrin alpha4
  • Integrins / analysis
  • Integrins / biosynthesis
  • Integrins / physiology*
  • Lung / embryology
  • Lung / growth & development
  • Lung / metabolism
  • Mice
  • Muscle Development
  • Muscle, Smooth, Vascular / embryology
  • Muscle, Smooth, Vascular / growth & development
  • Muscle, Smooth, Vascular / metabolism*
  • Myocardium / metabolism
  • Organ Specificity
  • Pregnancy
  • Vascular Cell Adhesion Molecule-1
  • Yolk Sac / metabolism


  • Cell Adhesion Molecules
  • Fibronectins
  • Integrins
  • Vascular Cell Adhesion Molecule-1
  • Integrin alpha4