A Scribble/Cdep/Rac pathway regulates follower cell crawling and cluster cohesion during collective border cell migration

Collective cell movements drive normal development and metastasis. Drosophila border cells move as a cluster of 6-10 cells, where the role of the Rac GTPase in migration was first established. Rac stimulates leading edge protrusions in most migratory cells. Upstream Rac regulators in leading border cell protrusions have been identified; however the regulation and function of Rac in follower cells is unknown. Here we show that Rac is required in all cells of the cluster and promotes follower cell motility. We identify a Rac guanine nucleotide exchange factor, Cdep, that also regulates follower cell movement and cluster cohesion. The tumor suppressors Scribble, Discs Large, and Lethal Giant Larva localize Cdep basolaterally and share phenotypes with Cdep. Relocalization of Cdep::GFP partially rescues Scrib knockdown, suggesting that Cdep is a major downstream effector of basolateral proteins. Thus, a Scrib/Cdep/Rac pathway promotes cell crawling and coordinated, collective migration in vivo.