Slit is the midline repellent for the robe receptor in Drosophila

Previous studies suggested that Roundabout (Robo) is a repulsive guidance r eceptor on growth cones that binds to an unknown midline ligand. Here we pr esent genetic evidence that Slit is the midline Robe ligand; a companion pa per presents biochemical evidence that Slit binds Robe. Slit is a large ext racellular matrix protein expressed by midline glia. In slit mutants, growt h cones enter the midline but never leave it; they abnormally continue to e xpress high levels of Robe while at the midline. slit and robe display dosa ge-sensitive genetic interactions, indicating that they function in the sam e pathway. slit is also required for migration of muscle precursors away fr om the midline. Slit appears to function as a short-range repellent control ling axon crossing of the midline and as a long-range chemorepellent contro lling mesoderm migration away from the midline.