Switching responses: spatial and temporal regulators of axon guidance

The ability of the axonal growth cone to switch between attraction and repulsion in response to guidance cues in the extracellular environment during nervous system development is fundamental to the precise wiring of complex neural circuits. Regulation of cell-surface receptors by means of transcriptional control, local translation, trafficking and proteolytic processing are powerful mechanisms to regulate the response of the growth cone. Important work has also revealed how intracellular signalling pathways, including calcium and cyclic nucleotide signalling, can alter the directional response elicited by a particular cue. Here, we describe how these multiple regulatory mechanisms influence growth cone turning behaviour. We focus on recent evidence that suggests a significant role for 14-3-3 adaptor proteins in modifying growth cone turning behaviour and mediating directional polarity switches during development. Characterizing how 14-3-3 s regulate growth cone signalling will provide invaluable insight into nervous system development and may facilitate the identification of novel targets for promoting nerve regeneration following injury.