Slit proteins bind robe receptors and have an evolutionarily conserved role in repulsive axon guidance

Extending axons in the developing nervous system are guided in part by repu lsive cues. Genetic analysis in Drosophila, reported in a companion to this paper, identifies the Slit protein as a candidate ligand for the repulsive guidance receptor Roundabout (Robo). Here we describe the characterization of three mammalian Slit homologs and show that the Drosophila Slit protein and at least one of the mammalian Slit proteins, Slit2, are proteolyticall y processed and show specific, high-affinity binding to Robe proteins. Furt hermore, recombinant Slit2 can repel embryonic spinal motor axons in cell c ulture. These results support the hypothesis that Slit proteins have an evo lutionarily conserved role in axon guidance as repulsive ligands for Robe r eceptors.