In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins

The restriction of intermingling between specific cell populations is cruci al for the maintenance of organized patterns during development. A striking example is the restriction of cell mixing between segments in the insect e pidermis' and the vertebrate hindbrain(2) that may enable each segment to m aintain a distinct identity. In the hindbrain, this is a result of differen t adhesive properties of odd- and even-numbered segments (rhombomeres)(3,4) , but an adhesion molecule with alternating segmental expression has not be en found. However, blocking experiments suggest that Eph-receptor tyrosine kinases may be required for the segmental restriction of cells(5). Eph rece ptors and their membrane-bound ligands, ephrins, are expressed in complemen tary rhombomeres(6) and, by analogy with their roles in axon pathfinding(7, 8), could mediate cell repulsion at boundaries. Remarkably, transmembrane e phrins can themselves transduce signals(9,10), raising the possibility that bi-directional signalling occurs between adjacent ephrin- and Eph-receptor -expressing cells. We report here that mosaic activation of Eph receptors l eads to sorting of cells to boundaries in odd-numbered rhombomeres, whereas mosaic activation of ephrins results in sorting to boundaries in even-numb ered rhombomeres. These data implicate Eph receptors and ephrins in the seg mental restriction of cell intermingling.