Synaptogenesis is a complex process that involves the coordinated assembly of pre- and postsynaptic compartments. Various extracellular pathways and cues have been shown to regulate synapse formation but here, on p. , David Van Vactor and colleagues show that the microRNA miR-8 controls synapse structure by repressing the actin regulator Enabled (Ena) and hence modulating synapse morphogenesis at the Drosophila neuromuscular junction (NMJ). The authors previously identified miR-8 as a potent regulator of NMJ architecture and presynaptic morphogenesis, and now find that Ena is direct target of miR-8 that is crucial for mediating its activity in synapse formation. Ena is enriched in the postsynaptic peribouton area surrounding the presynaptic compartment, and this localisation appears to depend on conserved actin-binding domains in the C-terminus of Ena. Further studies suggest that miR-8 controls NMJ architecture by inhibiting Ena expression and, hence, limiting the levels of postsynaptic Ena-dependent actin assembly, which in turn can regulate the expansion of presynaptic arbours. Together, these studies uncover a novel morphogenetic mechanism that coordinates the remodelling of pre- and post-synaptic compartments.
