Figure 1. Spatial segregation of Rho GTPase signaling in collective migration. (1) Sustained activation of Cdc42 and Rac upstream and downstream of ECM adhesion promotes protrusion formation. (2) Mechanocoupling of traction forces to the apical junctional complex. (3) Actomyosin contractility in conjunction with Rho activation by ECT2 and p114RhoGEF. (4) Increased Rac activation at cryptic lamellipodia by a combination of ECM-mediated Rac activation and Rac activation due to increased recycling and de novo formation of adherens junctions. In parallel, Rho activity is downregulated at cryptic lamellipodia by myosin IXA, which may also inhibit Rho activity at lateral junctions. (5) Rho activation at lateral junctions is inhibited by p190 RhoGAP, or via p120 catenin or Rnd3/RhoE.