Expanding roles for alpha 4 integrin and its ligands in development.
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.
Sheppard
A M
AM
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Onken
M D
MD
Rosen
G D
GD
Noakes
P G
PG
Dean
D C
DC
D000375:Aging / Q000502:physiology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D005314:Embryonic and Fetal Development; D004730:Endothelium, Vascular / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D015870:Gene Expression; D006321:Heart / Q000196:embryology / Q000254:growth & development; D039441:Integrin alpha4; D016023:Integrins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D011247:Pregnancy; D019010:Vascular Cell Adhesion Molecule-1; D015017:Yolk Sac / Q000378:metabolism
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4