Serial synapse formation through filopodial competition for synaptic seeding factors

Please always quote using this URN: urn:nbn:de:0297-zib-74397
  • 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.

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Author:M. Neset Özel, Abhishek Kulkarni, Amr Hasan, Josephine Brummer, Marian Moldenhauer, Ilsa-Maria Daumann, Heike Wolfenberg, Vincent J. Dercksen, F. Ridvan Kiral, Martin Weiser, Steffen Prohaska, Max von Kleist, P. Robin Hiesinger
Document Type:ZIB-Report
Tag:2-photon microscopy; brain wiring; filopodia; growth cone dynamics; model
MSC-Classification:60-XX PROBABILITY THEORY AND STOCHASTIC PROCESSES (For additional applications, see 11Kxx, 62-XX, 90-XX, 91-XX, 92-XX, 93-XX, 94-XX)
68-XX COMPUTER SCIENCE (For papers involving machine computations and programs in a specific mathematical area, see Section -04 in that area)
92-XX BIOLOGY AND OTHER NATURAL SCIENCES
CCS-Classification:I. Computing Methodologies
J. Computer Applications
PACS-Classification:80.00.00 INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY
Date of first Publication:2019/08/14
Series (Serial Number):ZIB-Report (19-45)
ISSN:1438-0064
Published in:Appeared in: Developmental Cell, 50(4), pp. 447-461, 2019
DOI:https://doi.org/10.1016/j.devcel.2019.06.014