EXPRESSION AND TYROSINE PHOSPHORYLATION OF EPH RECEPTORS SUGGEST MULTIPLE MECHANISMS IN PATTERNING OF THE VISUAL-SYSTEM

The EphA3 receptor tyrosine kinase has been implicated in guiding the axons of retinal ganglion cells as they extend in the optic tectum. A repulsive mechanism involving opposing gradients of the EphA3 receptor on retinal axons and its Ligands, ephrin-A2 and ephrin-A5, in the tec tum influences topographic mapping of the retinotectal projection. To investigate the overall role of the Eph family in patterning of the vi sual system, we have used in situ hybridization to localize nine Eph r eceptors in the chicken retina and optic tectum at Embryonic Day 8. Th ree of the receptors examined correspond to the novel chicken homologs of EphA2, EphA6, and EphA7. Unexpectedly, we found that many Eph rece ptors are expressed not only in retinal ganglion cells, but also in te ctal cells. In particular, EphA3 mRNA is prominently expressed in the anterior tectum, with a pattern reciprocal to that of ephrin-A2 and ep hrin-A5. Similarly, ephrin-A5 is expressed not only in tectal cells bu t also in the nasal retina, with a pattern reciprocal to that of its r eceptor EphA3 and partially overlapping with that of its other recepto r EphA4. Consistent with the even distribution of EphA4 and the polari zed distribution of EphA4 Ligands in the retina, probing EphA4 immunop recipitates from different sectors of the retina with anti-phosphotyro sine antibodies revealed spatial differences in receptor phosphorylati on. These complex patterns of expression and tyrosine phosphorylation suggest that Eph receptors and ephrins contribute to establishing topo graphy of retinal axons through multiple mechanisms, in addition to pl aying a role in intraretinal and intratectal organization. (C) 1998 Ac ademic Press.