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 f ound recently that these receptors have a second role, in embryogenesi s, where they mediate cell-cell interactions that are important for sk eletal muscle differentiation. Here, we present evidence of an expandi ng 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 hematopoieti c function in adult bone marrow. During angiogenesis in the lung, alph a 4 and VCAM-1 were found on mesenchyme that gives rise to vascular en dothelium and smooth muscle. alpha 4 persisted on the smooth muscle an d the endothelium of newly forming vessels where it colocalized with i ts extracellular matrix ligand, fibronectin (FN). These patterns sugge st several roles for alpha 4 integrins and their ligands in angiogenes is. alpha 4 was also found on neural crest derivatives where it coloca lized with FN. alpha 4 was expressed selectively on cells in the dorsa l root ganglia: it was apparent along ventral projections, but absent from dorsal projections, suggesting that alpha 4 integrins could be in volved in defining neuronal fates. Although VCAM-1 was not expressed o n most neural crest derivatives, it was found in the neural crest-deri ved outflow tract of the embryonic heart, where it colocalized with al pha 4. These results imply that alpha 4 integrins and their ligands co uld be important for migration or differentiation of neural crest. alp ha 4 was also expressed on embryonic retina and FN was found on induct ive mesenchyme surrounding the eye, suggesting a role for these protei ns 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 genera l ligand.