Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors

The robe gene in Drosophila was identified in a large-scale mutant screen for genes that control the decision by axons to cross the CNS midline. In robe mutants, too many axons cross and recross the midline. Here we show that robe encodes an axon guidance receptor that defines a novel subfamily of immunoglobulin superfamily proteins that is highly conserved from fruit flies to mammals. For those axons that never cross the midline, Robe is expressed on their growth cones from the outset; for the majority of axons that do cross the midline, Robe is expressed at high levels on their growth cones only after they cross the midline. Transgenic rescue experiments reveal that Robe can function in a cell-autonomous fashion. Robe appears to function as the gatekeeper controlling midline crossing.