Signaling of secreted semaphorins in growth cone steering

Despite a tremendous amount of progress in the identification and characterization of many new players as components of class 3 secreted semaphorin signaling in growth cone steering (Fig. 1), our understanding of the molecular mechanisms is far from complete. More questions remain to be answered: how are differential cytoskeletal changes within a growth cone achieved in response to semaphorins? What are the target(s) of cyclic nucleotide modulation? How does a growth cone make a reliable decision in response to a shallow gradient? And finally, how does a growth cone maintain its sensitivity to a decreasing concentration ofsemaphorins when it is growing away from the source? With a high degree of interest in the field with the development of novel technologies in analyzing growth cone steering, we expect to see a much more complete picture of semaphoring signaling in the near future.