Neural Circuits & Behavior Progress Report // Carolina Cela - A Comm2/Robo2/Slit signalling pathway regulates synaptic terminal arborisation

Synaptic terminal architectural maturation is a critical component of neuronal circuit amalgamation involving a compendium of morphological elaborations of synaptic structures. Analysis of the development of Drosophila neuromuscular junction (NMJ) synaptic terminals has primarily focused on the regulation of synaptic terminal size with other features of maturation remaining mostly unexplored. To address this deficit, we have investigated the process of synaptic terminal arborisation or branching. We find that, in contrast to previous assumptions, terminal branching does not take place throughout development, but instead occurs during a critical time window soon after embryos hatch. During this period the branching pattern of the synaptic terminal is defined and the majority of all terminal arbours form. To identify the genetic control of this process, we carried out a mutant screen and identified Commisureless 2 (comm2) as a novel key negative regulator of synapse arborisation. Comm2 shares homology to Comm, a well-described regulator of Robo signalling during neuronal axon guidance. We find that at synapses Comm2 regulates the Robo family member Robo2 which is required to promote terminal arborisation in response to a Slit ligand signal. Our results establish a new role for Slit/Robo signalling in mature neurons subsequent to the completion of axon guidance and establish the arborisation of synaptic terminals as an essential tightly regulated feature of synaptic structural consolidation.