Özel, M.N., Kulkarni, A., Hasan, A., Brummer, J., Moldenhauer, M., Daumann, I.M., Wolfenberg, H., Dercksen, V.J., Kiral, F.R., Weiser, M., Prohaska, S., von Kleist, M., Hiesinger, P.R. (2019). Serial Synapse Formation through Filopodial Competition for Synaptic Seeding Factors.  Dev. Cell 50(4): 447--461.e8.

FBrf0243277

Research paper

Following axon pathfinding, growth cones transition from stochastic filopodial exploration to the formation of a limited number of synapses. How the interplay of filopodia and synapse assembly ensures robust connectivity in the brain has remained a challenging problem. Here, we developed a new 4D analysis method for filopodial dynamics and a data-driven computational model of synapse formation for R7 photoreceptor axons in developing Drosophila brains. Our live data support a "serial synapse formation" model, where at any time point only 1-2 "synaptogenic" filopodia suppress the synaptic competence of other filopodia through competition for synaptic seeding factors. Loss of the synaptic seeding factors Syd-1 and Liprin-α leads to a loss of this suppression, filopodial destabilization, and reduced synapse formation. The failure to form synapses can cause the destabilization and secondary retraction of axon terminals. Our model provides a filopodial "winner-takes-all" mechanism that ensures the formation of an appropriate number of synapses.

PMC6702111 (PMC) (EuropePMC)