Neural map specification by gradients

Topographic maps, in which the spatial order of neurons maps smoothly onto their axonal target, are a central feature of neural wiring. Ephrins and Eph receptors are well accepted as graded labels for map development, enabling current studies into molecular principles of mapping. Ephrins regulate axon growth either positively or negatively, leading to models in which axons terminate at a neutral or optimum point in the gradient. Axonal competition ensures the target is filled. Ephrins and Ephs are typically expressed in complex overlapping patterns, with implications for signaling mechanisms, scale of internal map features, and coordinated interconnection of multiple mapping modules. Recent studies of Wnt3 and En-2 show that topographic axon guidance cues may be as diverse as molecules previously regarded as morphogens and transcription factors.