Topographic Mapping in Dorsoventral Axis of the Xenopus Retinotectal System Depends on Signaling through Ephrin-B Ligands

Abstract

Ephrin-B and EphB are distributed in matching dorsoventral gradients in the embryonic Xenopus visual system with retinal axons bearing high levels of ligand (dorsal) projecting to tectal regions with high receptor expression (ventral). In vitro stripe assays show that dorsal retinal axons prefer to grow on EphB receptor stripes supporting an attractive guidance mechanism. In vivo disruption of EphB/ephrin-B function by application of exogenous EphB or expression of dominant-negative ephrin-B ligand in dorsal retinal axons causes these axons to shift dorsally in the tectum, while misexpression of wild-type ephrin-B in ventral axons causes them to shift ventrally. These dorsoventral targeting errors are consistent with the hypothesis that an attractive mechanism that requires ephrin-B cytoplasmic domain is critical for retinotectal mapping in this axis.

In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

“…The physiologic importance of ephrin-B signaling has been confirmed by multiple in vivo observations using signalingdeficient mutants of Ephs, or ephrins to show the requirement for signals transduced inside the cell by ephrin-Bs (20)(21)(22)(23)(24)(25)(26). At a cellular level, ephrin-B activity results in cytoskeletal rearrangements (11), inhibition of chemokine-induced migration (15), and generation of adhesive (27)(28)(29) or repulsive responses (11,(19)(20)(21)(30)(31)(32)(33)(34)(35).…”

“…Although ephrin-Bs are widely expressed, most descriptions of their action focus on the processes of angiogenesis and nervous system organization (21)(22)(23)(24)(25)(26)(36)(37)(38)(39). Accumulating evidence now also suggests an important role for the EphB and ephrin-B molecules in malignancy.…”

Loss-of-Function Analysis of EphA Receptors in Retinotectal Mapping

“…RGM1 has recently been cloned as a molecule with topographically specific repellent activity in vitro and is expressed in an A-P gradient in chick tectum (Monnier et al, 2002). In addition, members of the B ephrin family and their receptors have been shown to be important for mapping of retinal axons along the dorsal-ventral axis (Hindges et al, 2002;Mann et al, 2002). It is also worth noting that, in addition to a forward signal through the Eph receptors, ephrins have the potential to act bidirectionally, with a reverse signal transduced through the ligands.…”

A novel feedback mechanism by Ephrin‐B1/B2 in T‐cell activation involves a concentration‐dependent switch from costimulation to inhibition

“…In contrast, Wu and colleagues have proposed promotional TCR costimulatory effects of all ephrin-Bs by using their original ephrin-B-Fc chimeric proteins [18][19][20]. However, the molecular basis for an Eph/ephrin system to inhibit or promote TCR signaling in each cell type remains unknown.In the central nervous system, it is now clear that Eph receptors have functional versatility, namely, both repulsive and attractive signals [21][22][23][24][25]. This bifunctional guidance cue may be regulated by developmental time and location, most likely characterized by the concentration and combination of the ligands.…”