During the morphogenesis of the Drosophila embryonic respiratory(tracheal) system, epithelial cells form a branched, tubular network that extends along stereotyped paths towards specific target tissues. Gallio et al. now report that Rhomboid 3 (Rho3) stops tracheal ganglionic branches (GBs)crossing the midline of the ventral nerve cord (VNC) in Drosophila(see p. 3605). Previous genetic analyses have uncovered several factors that guide the migration of the GBs, which provide oxygen to the VNC, including Slit, the main repulsive cue for axons at the midline. To identify additional factors,the researchers screened a collection of P-element mutant flies for GB pathfinding phenotypes. They report that Rho3, an intramembrane protease that activates epidermal growth factor receptor (Egfr) ligands, guides GBs independently of Slit, and propose that Rho3 activates one or more Egfr ligands, which then repel migrating GBs from the VNC midline.