Retinal ganglion cell axon guidance in the mouse optic chiasm: Expression and function of Robos and Slits

The ventral midline of the nervous system is an important choice point at w hich growing axons decide whether to cross and project contralaterally or r emain on the same side of the brain. In Drosophila, the decision to cross o r avoid the CNS midline is controlled, at least in part, by the Roundabout (Robo) receptor on the axons and its ligand, Slit, an inhibitory extracellu lar matrix molecule secreted by the midline glia. Vertebrate homologs of th ese molecules have been cloned and have also been implicated in regulating axon guidance. Using in situ hybridization, we have determined the expressi on patterns of robo1,2 and slit1,2,3 in the mouse retina and in the region of the developing optic chiasm, a ventral midline structure in which retina l ganglion cell (RGC) axons diverge to either side of the brain. The recept ors and ligands are expressed at the appropriate time and place, in both th e retina and the ventral diencephalon, to be able to influence RGC axon gui dance. In vitro, slit2 is inhibitory to RGC axons, with outgrowth of both i psilaterally and contralaterally projecting axons being strongly affected. Overall, these results indicate that Robos and Slits alone do not directly control RGC axon divergence at the optic chiasm and may additionally functi on as a general inhibitory guidance system involved in determining the rela tive position of the optic chiasm at the ventral midline of the developing hypothalamus.