Fig. 7.

Model for α3-integrin and traction force signaling during definitive endoderm differentiation. During definitive endoderm differentiation, activin A binds to TGF-β receptors, resulting in the activation of α5β1-integrin-mediated contractility and phosphorylation of SMAD2 and SMAD3. SMAD7, a competitive inhibitor of SMAD2 and SMAD3 phosphorylation, and α5β1-integrin are inhibited by α3β1-integrin-mediated laminin sensing. Treatment with blebbistatin, an inhibitor of myosin activity and therefore traction forces, prevents accumulation of the SMAD2–SMAD3–SMAD4 complex within the nucleus.