Waltzing Mice Add a New Twist to the Function of EphB2

the ephrinB " ligands " are the acting receptors that trans-to the Function of EphB2 duce a " reverse " signal from the midline to the axons. Consistent with a role for ephrins in midline guidance, Nakagawa and colleagues showed recently that Eph/ ephrin signaling may also be required to set up the pat-The Eph receptor tyrosine kinases and their ligands, the tern of crossed and uncrossed projections at the Xeno-ephrins, initially caught the attention of neurobiologists pus optic chiasm (Nakagawa et al., 2000). At the op-with the discovery that they are involved in the formation tic chiasm, axons from specific regions of the retina of topographic projections in the retinotectal system either cross, projecting to the contralateral side of the (recently reviewed by Flanagan and Vanderhaeghen, brain, or continue projecting ipsilaterally. colleagues showed that ephrin-B is expressed at the 1999). Sperry, in his chemoaffinity hypothesis, proposed chiasm, and EphB receptors are expressed by retinal that gradients of matching labels in the projecting and axons. Furthermore, misexpression of ephrin-B is suffi-target fields allowed axons to project to topographically cient to cause EphB-expressing axons to project ipsilat-correct positions. After decades of searching, the Eph erally. In this issue, Cowan and colleagues report that receptors (EphRs) and their ligands, the ephrins, were the EphBs also guide the pathfinding of yet another popu-identified as the potential candidates for the molecules lation of midline-crossing axons: the IEEs, a population of proposed by Sperry's chemoaffinity hypothesis, and in-axons that modulate sensory input to the inner ear. deed both in vitro and in vivo studies in the chick and Interestingly, the role of ephrins/EphRs in guiding mouse visual systems support a role for these families these crossing axons to the ear represents yet another in topographic map formation. Branching off from these twist on how ephrins/EphB work to steer axons at the initial studies in the retinotectal system, the ephrins have midline. IEEs that have their cell bodies located near now been shown to act as contact repellents for a wide the floor plate in rhombomere 4 are a heterogeneous variety of axons and cell types. While topographic map-population of axons, as some of them project to the ping in the visual system is still the most frequently used ipsilateral ear, whereas others cross the midline to pro-model system to study the role of the Eph receptor ject to the contralateral ear. In mice lacking the …