During development, neurons are guided by multiple guidance molecules and their receptors, but how developing neurons integrate these different guidance cues to form neural circuits is unclear. Alex Kolodkin's team has been examining the roles of plexins – receptors for the semaphorin guidance cues–in the developing Drosophila nervous system. On , these researchers report important new insights into how the multiple components of the semaphorin system interact by showing that the two fly plexins (PlexA and PlexB) have both distinct and overlapping functions in central and peripheral axon pathfinding. Their observation that PlexA and PlexB physically associate in vivo and can use common downstream signalling pathways provides an explanation for their overlapping functions. The researchers' discovery that PlexB is a receptor for the secreted semaphorin Sema-2a–PlexA is a receptor for the transmembrane semaphorin Sema-1a–suggests that the distinct roles of the two plexins in axon pathfinding could be mediated by interactions with different semaphorins. Together, these results reveal how complex neuronal guidance is determined at different molecular levels.
