Critical roles for EphB and ephrin-B bidirectional signaling in retinocollicular mapping

Graded expression of EphB and ephrin-B along the dorsoventral axis of the retina indicates a role for these bidirectional signaling molecules in dorsoventral-mediolateral retinocollicular mapping. While previous studies have implicated EphB2 forward signaling in mice, the intracellular component of EphB2 essential for retinocollicular mapping is unknown as are the roles for EphB1, ephrin-B1, and ephrin-B2. Here we show that EphB2 tyrosine kinase catalytic activity and EphB1 intracellular signaling are key mediators of ventral-temporal retinal ganglion cell axon retinocollicular mapping, by likely interacting with ephrin-B1 in the superior colliculus. We further elucidate roles for the ephrin-B2 intracellular domain in retinocollicular mapping and present the unexpected finding that both dorsal and ventral-temporal retinal ganglion cell axons utilize reverse signaling for topographic mapping. These data demonstrate that both forward and reverse signaling initiated by EphB:ephrin-B interactions play a major role in dorsoventral retinal ganglion cell axon termination along the mediolateral axis of the superior colliculus.