Interaxonal Interaction Defines Tiled Presynaptic Innervation in C. elegans

SummaryCellular interactions between neighboring axons are essential for global topographic map formation. Here we show that axonal interactions also precisely instruct the location of synapses. Motoneurons form en passant synapses in Caenorhabditis elegans. Although axons from the same neuron class significantly overlap, each neuron innervates a unique and tiled segment of the muscle field by restricting its synapses to a distinct subaxonal domain—a phenomenon we term synaptic tiling. Using DA8 and DA9 motoneurons, we found that the synaptic tiling requires the PlexinA4 homolog, PLX-1, and two transmembrane semaphorins. In the plexin or semaphorin mutants, synaptic domains from both neurons expand and overlap with each other without guidance defects. In a semaphorin-dependent manner, PLX-1 is concentrated at the synapse-free axonal segment, delineating the tiling border. Furthermore, plexin inhibits presynapse formation by suppressing synaptic F-actin through its cytoplasmic GTPase-activating protein (GAP) domain. Hence, contact-dependent, intra-axonal plexin signaling specifies synaptic circuits by inhibiting synapse formation at the subcellular loci.Video Abstract To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowHelp with MP4 filesOptionsDownload video (77248 K)

► Axon-axon interactions studied in vivo ► We describe and molecularly characterize synaptic tiling ► Role of sema/plexin signaling in synaptic patterning independent of axon guidance ► Extracellular cues inhibit synapse formation through regulating synaptic F-actin