Fibronectin receptor functions in embryonic cells deficient in α₅β₁ integrin can be replaced by α(v) integrins

α₅β₁ integrin mediates cell adhesion to extracellular matrix by interacting with fibronectin (FN). Mouse lines carrying null mutations in genes encoding either the α₅ integrin subunit or FN have been generated previously. Both mutations are embryonic lethal with overlapping defects, but the defects of α₅-null embryos are less severe. Primary embryonic cells lacking α₅β₁ are able to adhere to FN, form focal contacts, migrate on FN, and assemble FN matrix. These results suggest the involvement of (an)other FN receptor(s). In this study, we examined functions of α₄β₁ and α(v) integrins in embryonic cells lacking α₅β₁. Our analysis of cells lacking both α₄β₁ and α₅β₁ showed that α₄β₁ is also not required for these FN-dependent functions. Using α(v)-specific blocking reagents, we showed that α(v) integrins are required for α₅-null cells, but not wild-type cells, to adhere and spread on FN. Our data also showed that, although the expression levels of α(v) integrins on the wild-type and α₅-null cells are similar, there is an increase in recruitment of α(v) integrins into focal contacts in α₅-null cells plated on FN, indicating that α(v) integrins can compensate functionally for the loss of α₅β₁ in focal contacts of α₅-null cells. Finally, our data suggested possible roles for α(v) integrins in replacing the role of α₅β₁ in FN matrix assembly in vitro and in FN-dependent embryonic functions in vivo.