Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons

The olfactory bulb plays a central role in olfactory information processing through its connections with both peripheral and cortical structures. Axon s projecting from the olfactory bulb to the telencephalon are guided by a r epulsive activity in the septum. The molecular nature of the repellent is n ot known. We report here the isolation of vertebrate homologs of the Drosop hila slit gene and show that Slit protein binds to the transmembrane protei n Roundabout (Robo). Slit is expressed in the septum whereas Robe is expres sed in the olfactory bulb. Functionally, Slit acts as a chemorepellent for olfactory bulb axons. These results establish a ligand-receptor relationshi p between two molecules important for neural development, suggest a role fo r Slit in olfactory bulb axon guidance, and reveal the existence of a new f amily of axon guidance molecules.