Genetic analysis of ephrin-A2 and ephrin-A5 shows their requirement in multiple aspects of retinocollicular mapping

Ephrin-A2 and -A5 are thought to be anteroposterior mapping labels for the retinotectal/retinocollicular projection. Here, gene disruptions of both th ese ephrins are characterized. Focal retinal labeling reveals moderate map abnormalities when either gene is disrupted. Double heterozygotes also have a phenotype, showing an influence of absolute levels. In vitro assays indi cate these ephrins are required for repellent activity in the target and al so normal responsiveness in the retina. In double homozygotes, anteroposter ior order is almost though not completely lost. Temporal or nasal retinal l abelings reveal quantitatively similar but opposite shifts, with multiple t erminations scattered widely over the target. These results indicate an axo n competition mechanism for mapping, with a critical role for ephrins as an teroposterior topographic labels. Dorsoventral topography is also impaired, showing these ephrins are required in mapping both axes.