Modulation of EphA receptor function by coexpressed EphrinA ligands on retinal ganglion cell axons

The Eph family is thought to exert its function through the complementary e xpression of receptors and ligands. Here, we show that EphA receptors coloc alize on retinal ganglion cell (RGC) axons with EphA ligands, which are exp ressed in a high-nasal-to-low-temporal pattern. In the stripe assay, only t emporal axons are normally sensitive for repellent axon guidance cues of th e caudal tectum. However, overexpression of ephrinA ligands on temporal axo ns abolishes this sensitivity, whereas treatment with PI-PLC both removes e phrinA ligands from retinal axons and induces a striped outgrowth of former ly insensitive nasal axons. In vivo, retinal overexpression of ephrinA2 lea ds to topographic targeting errors of temporal axons. These data suggest th at differential ligand expression on retinal axons is a major determinant o f topographic targeting in the retinotectal projection.