The N-terminal leucine-rich regions in Slit are sufficient to repel olfactory bulb axons and subventricular zone neurons

The Slit proteins are a new family of secreted guidance cues involved in ax on guidance and neuronal migration. Each mammalian Slit protein contains >1 400 amino acid residues, with four leucine-rich regions (LRRs), nine epider mal growth factor repeats, a laminin G domain, and a C-terminal cysteine-ri ch domain. A receptor for Slit is the transmembrane protein Roundabout (Rob o), whose extracellular part contains five Ig domains and three fibronectin type III repeats. We report here that the LRRs in Slit are sufficient for binding to the Ig domains of Robo. Mutant forms of Slit containing only the LRRs function as chemorepellents for axons projecting from the olfactory b ulb both in vitro and in the telencephalon. The LRRs can repel neurons migr ating from the anterior subventricular zone (SVZa) to the olfactory bulb in brain slices isolated from neonatal rodents. However, the LRRs do not show repulsive effects on the SVZa neurons migrating in collagen gels. Our resu lts indicate that the same LRRs are sufficient for guiding both axon projec tion and neuronal migration and suggest that the other regions in the Slit proteins may be involved in regulating the diffusion and distribution of th e Slit proteins. The fact that the same domains are involved in guiding axo n projection and neuronal migration further strengthens the idea of a conse rved guidance mechanism for these important processes.