Target-independent ephrina/EphA-mediated axon-axon repulsion as a novel element in retinocollicular mapping

EphrinAs and EphAs play critical roles during topographic map formation in the retinocollicular projection; however, their complex expression patterns in both the retina and superior colliculus (SC) have made it difficult to uncover their precise mechanisms of action. We demonstrate here that growth cones of temporal axons collapse when contacting nasal axons in vitro, and removing ephrinAs from axonal membranes by PI-PLC treatment abolishes this response. In conditional knockout mice, temporal axons display no major targeting defects when ephrinA5 is removed only from the SC, but substantial mapping defects were observed when ephrinA5 expression was removed from both the SC and from the retina, with temporal axons invading the target areas of nasal axons. Together, these data indicate that ephrinA5 drives repellent interactions between temporal and nasal axons within the SC, and demonstrates for the first time that target-independent mechanisms play an essential role in retinocollicular map formation in vivo.