Slit2 is a repellent for retinal ganglion cell axons

We set out to isolate inhibitory guidance cues that affect retinal ganglion cell (RGC) axons in vitro and that could potentially be involved in RGC pa thfinding decisions. Here we describe the biochemical purification of an RG C growth cone collapsing factor from bovine brain membranes and its identif ication as Slit2. Recombinant human Slit2 collapses and repels RGC growth c ones from all quadrants of the chick retina. In the developing mouse visual system, slit2 is expressed in the eye, in the optic stalk, and in the vent ral diencephalon. Slit2 expression is strong in anterior ventral diencephal ic structures but is absent from the ventral midline where the optic chiasm forms. The putative receptors for Slits, robo1 and robo2, are expressed in the inner retinal layer in which RGCs are located. A comparison of the exp ression patterns of Slit2 and retinal axon trajectories suggests that slit2 acts as a short range repellent for retinal ganglion cell axons.