Two homeobox genes define the domain of EphA3 expression in the developingchick retina

Graded expression of the Eph receptor EphA3 in the retina and its two ligan ds, ephrin A2 and ephrin A5 in the optic tectum, the primary target of reti nal axons, have been implicated in the formation of the retinotectal projec tion map. Two homeobox containing genes, SOHo1 and GH6, are expressed in a nasal-high, temporal-low pattern during early retinal development, and thus in opposing gradients to EphA3. Retroviral misexpression of SOHo1 or GH6 c ompletely and specifically repressed EphA3 expression in the neural retina, but not in other parts of the central nervous system, such as the optic te ctum, Under these conditions, some temporal ganglion cell axons overshot th eir expected termination zones in the rostral optic tectum, terminating abe rrantly at more posterior locations. However, the majority of ganglion cell axons mapped to the appropriate rostrocaudal locations, although they form ed somewhat more diffuse termination zones. These findings indicate that ot her mechanisms, in addition to differential EphA3 expression in the neural retina, are required for retinal ganglion axons to map to the appropriate r ostrocaudal locations in the optic tectum, They further suggest that the co ntrol of topographic specificity along the retinal nasal-temporal axis is s plit into several independent pathways already at a very early time in deve lopment.