CELLULAR-LOCALIZATION OF EPHRIN-A2, EPHRIN-A5, AND OTHER FUNCTIONAL GUIDANCE CUES UNDERLIES RETINOTOPIC DEVELOPMENT ACROSS SPECIES

Avian retinotectal and rodent retinocollicular systems are general mod el systems used to examine developmental processes that underpin topog raphically organized neuronal circuits. The two systems rely on guidan ce components to establish their precise retinotopic maps, but many ce llular events differ during their development. For example, compared w ith the chick, a generally less restricted outgrowth pattern is observ ed when retinae innervate their targets in rodents. Cellular or molecu lar distributions of guidance components may account for such differen ces in retinotopic development across species. Candidate repellent mol ecules, such as ephrin-A2 and ephrin-A5, have been cloned in both chic k and rodents; however, it has not yet been shown in rodents that livi ng cells express sufficient amounts of any repellent components to det er outgrowth. We used a coculture assay that gives cellular resolution of retino-target interactions and demonstrate that living, caudal sup erior colliculus cells selectively prevent extension of axons from tem poral regions of the retinae. Time-lapse video microscopy revealed the cellular localization of permissive and repulsive guidance components in rodents, which differed from that in chick. To analyze the potenti al molecular basis for these differences, we investigated the function and localization of ephrin-A2 and -A5. Cells transfected with ephrin- A2 and -A5 selectively repelled retinal axons. Ephrin-A2 and -A5 RNA e xpression patterns differed across cell populations and between specie s, suggesting molecular mechanisms and key cellular interactions that may underlie fundamental differences in the development of retinotecta l and retinocollicular maps.