ABSTRACT: Fibronectin and integrins play crucial roles in a variety of morphogenetic processes, in which they mediate cell adhesion, migration, and signal transduction. They induce hierarchical transmembrane organization of cytoskeletal and signaling molecules into multimolecular complexes of more than 30 proteins. Organization of these complexes is a synergistic process dependent on integrin aggregation and occupancy, as well as tyrosine phosphorylation. Integrins also cooperate with growth-factor receptors to enhance signaling. Fibronectin and integrins induce a variety of downstream effects, including enhanced transcription factor activity, induction of over 30 genes (>half novel), and altered expression of over 100 proteins. Fibronectin and integrins therefore trigger a hierarchy of signaling responses involved in regulating processes crucial for normal morphogenesis, including cell adhesion, migration, and specific gene expression.