Axon guidance in the mouse optic chiasm: Retinal neurite inhibition by Ephrin "A"-expressing nypothalamic cells in vitro

In the mammalian visual system, retinal axons undergo temporal and spatial rearrangements as they project bilaterally to targets on the brain. Retinal axons cross the neuraxis to form the optic chiasm on the hypothalamus in a position defined by overlapping domains of regulatory gene expression. How ever, the downstream molecules that direct these processes remain largely u nknown. Here we use a novel in vitro paradigm to study possible roles of th e Eph family of receptor tyrosine kinases in chiasm formation, in vivo, Eph receptors and their ligands distribute in complex patterns in the retina a nd hypothalamus. In vitro, retinal axons are inhibited by reaggregates of i solated hypothalamic, but not dorsal diencephalic or cerebellar cells. Furt hermore, temporal retinal neurites are more inhibited than nasal neurites b y hypothalamic cells. Addition of soluble EphA5-Fc to block Eph "A" subclas s interactions decreases both the inhibition and the differential response of retinal neurites by hypothalamic reaggregates. These data show that isol ated hypothalamic cells elicit specific, position-dependent inhibitory resp onses from retinal neurites in culture. Moreover, these responses are media ted, in part, by Eph interactions. Together with the in vivo distributions, these data suggest possible roles for Eph family members in directing reti nal axon growth and/or reorganization during optic chiasm formation. (C) 20 00 Academic Press.