INTERACTIONS OF EPH-RELATED RECEPTORS AND LIGANDS CONFER ROSTROCAUDALPATTERN TO TRUNK NEURAL CREST MIGRATION

Background: In the trunk of avian embryos, neural crest migration thro ugh the somites is segmental, with neural crest cells entering the ros tral half of each semitic sclerotome but avoiding the caudal half. Lit tle is known about the molecular nature of the cues - intrinsic to the somites - that are responsible for this segmental migration of neural crest cells. Results: We demonstrate that Eph-related receptor tyrosi ne kinases and their ligands are essential for the segmental migration of avian trunk neural crest cells through the somites. EphB3 localize s to the rostral half-sclerotome, including the neural crest, and the ligand ephrin-B1 has a complementary pattern of expression in the caud al half-sclerotome, To test the functional significance of this striki ng asymmetry, soluble ligand ephrin-B1 was added to interfere with rec eptor function in either whole trunk explants or neural crest cells cu ltured on alternating stripes of ephrin-B1 versus fibronection. Neural crest cells in vitro avoided migrating on lanes of immobilized ephrin -B1; the addition of soluble ephrin-B1 blocked this inhibition. Simila rly, in whole trunk explants, the metameric pattern of neural crest mi gration was disrupted by addition of soluble ephrin-B1, allowing entry of neural crest cells into caudal portions of the sclerotome. Conclus ions: Both in vivo and in vitro, the addition of soluble ephrin-B1 res ults in a loss of the metameric migratory pattern and a disorganizatio n of neural crest cell movement. These results demonstrate that Eph-fa mily receptor tyrosine kinases and their transmembrane ligands are inv olved in interactions between neural crest and sclerotomal cells, medi ating an inhibitory activity necessary to constrain neural precursors to specific territories in the developing nervous system.