Serial synapse formation through filopodial competition for synaptic seeding factors

Ozel, M. N.; Kulkarni, A.; Hasan, A.; Brummer, J.; Moldenhauer, M.; Daumann, I.-M.; Wolfenberg, H.; Dercksen, V.; Kiral, F. R.; Weiser, M.; Prohaska, S.; von Kleist, M.; Hiesinger, P. R.

doi:10.1101/506378

bioRxiv · 10.1101/506378

Serial synapse formation through filopodial competition for synaptic seeding factors

Ozel, M. N.·Kulkarni, A.·Hasan, A.·Brummer, J.·Moldenhauer, M.·Daumann, I.-M.·Wolfenberg, H.·Dercksen, V.·Kiral, F. R.·Weiser, M.·Prohaska, S.·von Kleist, M.·Hiesinger, P. R.

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Abstract

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- 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.

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Ozel, M. N., Kulkarni, A., Hasan, A., Brummer, J., Moldenhauer, M., Daumann, I.-M., Wolfenberg, H., Dercksen, V., Kiral, F. R., Weiser, M., Prohaska, S., von Kleist, M., Hiesinger, P. R.. 2018-12-26. Serial synapse formation through filopodial competition for synaptic seeding factors. https://doi.org/10.1101/506378

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