Ephrin/Eph signaling in axon guidance

Abstract Animal behavior and cognition arise as a result of the developmental wiring of neural circuits in which axonal growth cones are guided by specialized ligand–receptor systems. Given the high complexity of even the simplest connectomes, the number of different guidance molecules is minute. This small number of genetically encoded cues generates most of the complexity of neuronal wiring through its deployment in sophisticated qualitative and quantitative combinations, much like the limited repertoire of notes gives rise to the prodigious richness of musical works. The ephrin/Eph system forms a major part of the guidance molecule repertoire. Its high versatility is due to variegated signaling options. These include the unique fact that ephrin/Eph signaling can operate in two fundamentally different ways, in a binary or a proportional mode. The binary mode operates when one of the two possible guidance alternatives is selected. The proportional mode, in contrast, allows for distinguishing thousands of subtly different addresses, such as those underlying somatotopic or retinotopic maps.