Axon Guidance and Repulsion. The Molecular Code of Social Life in the Brain

The generation of a functional nervous system is dependent on precise pathfinding of axons during their development. This pathfinding is directed by the distribution of local and long-range guidance cues. Gradients of long-range guidance cues have been associated with growth cone function for over a hundred years, but their developmental roles are still poorly understood. Here we review the developmental roles and the complex intracellular signaling pathways enabling chemoattractive or repulsive axon-guidance molecules like netrins, semaphorins and ephrins to regulate axon growth. Recent research findings suggest that these molecules signal through specific receptors leading to local cytoskeletal rearrangements in the growth cone or cell leading edge; and through intracellular kinases, which have the potential to alter gene expression changes in the developing neuron. In addition, we also summarize the increasing body of knowledge on their roles in the inhibition of axon regeneration after adult lesions in the central and peripheral nervous system.