Roles of Eph receptors and ephrins in segmental patterning

Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, ha ve key roles in patterning and morphogenesis. Interactions between these mo lecules are promiscuous, but largely fall into two groups: EphA receptors b ind to glycosylphosphatidyl inositol-anchored ephrin-A ligands, and EphB re ceptors bind to transmembrane ephrin-B proteins. Ephrin-B proteins transduc e signals, such that bidirectional signalling can occur upon interaction wi th the Eph receptor. In man); tissues, there are complementary and overlapp ing expression domains of interacting Eph receptors and ephrins. An importa nt role of Eph receptors and ephrins is to mediate cell contact-dependent r epulsion, and this has been implicated ill the pathfinding of axons and neu ral crest cells, and the restriction of cell intermingling between hindbrai n segments. Studies in an in vitro system show that bidirectional activatio n is required to prevent intermingling between cell populations, whereas un idirectional activation can restrict cell communication via gap junctions. Recent work indicates that Eph receptors can also upregulate cell adhesion, but the biochemical basis of repulsion versus adhesion responses is unclea r. Eph receptors and ephrins have thus emerged as key regulators that, in p arallel with cell adhesion molecules, underlie the establishment and mainte nance of patterns of cellular organization.