Figure 2. Eph/ephrin signaling provides support and guidance for migrating cells during development.

(A) Ephrin-Bs have been implicated in both cranial and trunk neural crest cell (NCC) migration. Recent genetic evidence in mice suggests that the role of ephrin-B2 in cranial NCC migration is secondary to its role in the vasculature, and therefore that ephrin-B2 signaling in this context acts not as a guidance cue, but rather as a supplier of support and nutrients critical to NCC survival. During trunk NCC migration, ephrin-B1 (in chick) or ephrin-B2 (in mouse) is thought to act as a guidance cue for migrating cells, with their expression in the posterior half of the somite restricting migration of EphB-expressing NCCs to the anterior half of the somite. (B) The secreted neuronal guidance cue Reelin interacts biochemically with Eph receptors, and compound EphB receptor mutant mice as well as compound ephrin-B mutant mice have reeler (Reln^−/−)-like neuronal migration phenotypes in both the cortex and hippocampus. Although many Eph or ephrin compound mutant phenotypes are not as severe as Reln^−/− phenotypes, this raises the intriguing possibility that Eph/ephrin signaling and Reelin signaling may synergize to promote neuronal migration in the cortex and hippocampus. (C) EphB/ephrinB signaling, with EphB3b expressed in the lateral plate mesoderm (LPM) and ephrin-B1 expressed in the hepatoblasts, is essential for correct asymmetric positioning of the liver during zebrafish development. NCC, neural crest cell; LPM, lateral plate mesoderm.