INTRODUCTION Among the earliest events in visual system development are RGC axon pathfinding within the retina to the optic disc and subsequent axon growth through the disc into the optic stalk to form the optic nerve. Guidance mechanisms

Among the earliest events in visual system development are RGC axon pathfinding within the retina to the optic disc and subsequent axon growth through the disc into the optic stalk to form the optic nerve. Guidance mechanisms underlying these pathfinding tasks are not completely understood. Studies demonstrate that at the optic disc, the axon guidance molecule netrin-1 controls, to a large extent, proper RGC axon growth through this exit point into the optic nerve (Deiner et al., 1997). However, since RGC axons in animals lacking netrin-1 or its receptor DCC are still able to find their way to the disc, guidance cues underlying pathfinding to the disc are distinct from those which mediate RGC axon growth through the disc and into the nerve. During pathfinding to the disc, RGC axons express Ig-CAMs (Bartsch et al., 1989; Paschke et al., 1992; Silver and Rutishauser, 1984), and anti-Ig-CAM antibody injections intraocularly in vivo, or applied onto retinal eye cup preparations in vitro, cause abnormal intra-retinal axon trajectories (Brittis et al., 1995; Ott et al., 1998). However, these perturbations do not affect all RGC axons, suggesting that additional guidance cues are involved in pathfinding to the optic disc. Further along the visual pathway, the topographic mapping of RGC axons in the superior colliculus appears to depend on inhibitory interactions between Eph receptor tyrosine kinases on RGC axons and target derived ephrin ligands. Eph receptors belong to either the A or B subfamily which bind respectively to the A (GPI-linked) or B (transmembrane) subfamily of ephrin ligands (Brambilla et al., 1996; Eph Nomenclature Committee, 1997; Flanagan and Vanderhaeghen, 1998; Gale et al., 1996; Himanen et al., 1998). Experimental evidence indicates that the anterior-posterior orientation of the retinocollicular map is dependent on EphA receptors expressed in a nasal-temporal retinal gradient and an opposing anteriorposterior gradient of ephrin-A ligands in the target (Cheng et 1231 Development 127, 1231-1241 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV4289