A planar polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia

Tissue fluidification and collective motility are pivotal in regulating embryonic morphogenesis, wound heal-ing, and tumor metastasis. These processes frequently require that each cell constituent of a tissue coordi-nates its migration activity and directed motion through the oriented extension of lamellipodium cell protru-sions, promoted by RAC1 activity. While the upstream RAC1 regulators in individual migratory cells or leader cells during invasion or wound healing are well characterized, how RAC1 is controlled in follower cells re-mains unknown. Here, we identify a MYO6-DOCK7 axis essential for spatially restricting RAC1 activity in a planar polarized fashion in model tissue monolayers. The MYO6-DOCK7 axis specifically controls the exten-sion of cryptic lamellipodia required to drive tissue fluidification and cooperative-mode motion in otherwise solid and static carcinoma cell collectives.