Generation of neuromuscular specificity in Drosophila: novel mechanisms revealed by new technologies

The Drosophila larval neuromuscular system is one of the best-characterized model systems for axon targeting. In each abdominal hemisegment, only 36 identified motor neurons form synaptic connections with just 30 target muscles in a highly specific and stereotypic manner. Studies in the 1990s identified several cell-surface and secreted proteins that are expressed in specific muscles and contribute to target specificity. Emerging evidence suggests that target selection is determined not only by attraction to the target cells but also by exclusion from non-target cells. Proteins with leucine-rich repeats (LRR proteins) appear to be a major molecular family of proteins responsible for the targeting. While the demonstrated roles of the target-derived cues point to active recognition by presynaptic motor neurons, postsynaptic muscles also reach out and recognize specific motor neurons by sending out cellular protrusions called myopodia. Simultaneous live imaging of myopodia and growth cones has revealed that local and mutual recognition at the tip of myopodia is critical for selective synapse formation. A large number of candidate target cues have been identified on a single muscle, suggesting that target specificity is determined by the partially redundant and combinatorial function of multiple cues. Analyses of the seemingly simple neuromuscular system in Drosophila have revealed an unexpected complexity in the mechanisms of axon targeting.