Neuronal connections are arranged topographically such that the spatial org
anization of neurons is preserved by their termini in the targets. During t
he development of topographic projections, axons initially explore areas mu
ch wider than the final targets, and mistargeted axons are pruned later. Th
e molecules regulating these processes are not known, We report here that t
he ligands of the Eph family tyrosine kinase receptors may regulate both th
e initial outgrowth and the subsequent pruning of axons, In the presence of
ephrins, the outgrowth and branching of the receptor-positive hippocampal
aliens are enhanced. However, these axons are induced later to degenerate.
These observations suggest that the ephrins and their receptors may regulat
e topographic map formation by stimulating axonal arborization and by pruni
ng mistargeted axons.