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Serial synapse formation through filopodial competition for synaptic seeding factors

  • 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 a single 'synaptogenic' filopodium suppresses 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, which is sufficient to cause the destabilization of entire axon terminals. Our model provides a filopodial 'winner-takes-all' mechanism that ensures the formation of an appropriate number of synapses.
Author:Mehmet Neset Ozel, Abhishek Kulkarni, Amr Hasan, Josephine Brummer, Marian Moldenhauer, Ilsa-Maria Daumann, Heike Wolfenberg, Vincent J. DercksenORCiD, Ferdi Ridvan Kiral, Martin WeiserORCiD, Steffen Prohaska, Max von Kleist, Peter Robin Hiesinger
Document Type:Article
Parent Title (English):Developmental Cell
First Page:447
Last Page:461
Year of first publication:2019
Published in:appeared also as bioRxiv preprint https://doi.org/10.1101/506378
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