Implication of retinal EphA4 in refinementof collicular visual maps

EphA/ephrin-A signaling has been demonstrated to mediate the establishment of the topographic visual map: In mammals EphA5 and EphA6 are expressed in a high-temporal to low-nasal gradient in the retina while ephrin-A5 is expressed in a high-caudal low-rostral gradient in the superior colliculus. In contrast, EphA4, another member of the EphA family, is homogenously expressed in retinal ganglion cells (RGCs) and its role in retinal development has not been clarified. In this study we investigated the role of EphA4 during the development of the visual system in mice. We found that EphA4 mutant mice show larger and extended ramifications of RGC arbor terminals in the visual targets compared to control mice. Conversely we determined that ectopic expression of EphA4 in the retina induces aberrant adhesion of axon terminals at the visual targets, but also of RGCs in the retina. We demonstrated that EphA4/ephrin-B1 forward signalling is responsible for this adhesive phenotype. Together with previous reports, our results strongly suggest that axon terminals coming from the retina activate EphA4 when encountering ephrin-B1 at the visual targets, to modulate axon branches adhesion during the refinement phase of topographic visual mapping