Local F-actin network links synapse formation and axon branching.

Axonal branching and synapse formation are tightly linked developmental events during the establishment of synaptic circuits. Newly formed synapses promote branch initiation and stability. However, little is known about molecular mechanisms that link these two processes. Here, we show that local assembly of an F-actin cytoskeleton at nascent presynaptic sites initiates both synapse formation and axon branching. We further find that assembly of the F-actin network requires a direct interaction between the synaptic cell adhesion molecule SYG-1 and a key regulator of actin cytoskeleton, the WVE-1/WAVE regulatory complex (WRC). SYG-1 cytoplasmic tail binds to the WRC using a consensus WRC interacting receptor sequence (WIRS). WRC mutants or mutating the SYG-1 WIRS motif leads to loss of local F-actin, synaptic material, and axonal branches. Together, these data suggest that synaptic adhesion molecules, which serve as a necessary component for both synaptogenesis and axonal branch formation, directly regulate subcellular actin cytoskeletal organization.