Integration of guidance cues: parallel signaling and crosstalk

Growing axons are exposed to various guidance cues en route to their targets. Although many guidance molecules have been identified and their effects on axon behavior extensively studied, how axons react to combinations of signals remains largely unexplored. We review recent studies investigating the combined actions of guidance cues present at the same choice points. Two main scenarios are emerging from these studies: parallel signaling and crosstalk between guidance systems. In the first case, cues act in an additive manner, whereas in the second case the outcome is non-additive and differs from the sum of individual effects, suggesting more complex signal integration in the growth cone. Some of the molecular mechanisms underlying these interactions are beginning to be unraveled.