Serial Synapse Formation through Filopodial Competition for Synaptic Seeding Factors.

Autor:	Özel MN; Division of Neurobiology, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany; Neuroscience Graduate Program, UT Southwestern Medical Center Dallas, Dallas, TX 75390, USA., Kulkarni A; Division of Neurobiology, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany., Hasan A; Division of Neurobiology, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany., Brummer J; Department of Visual Data Analysis, Zuse Institute Berlin, 14195 Berlin, Germany., Moldenhauer M; Computational Medicine and Numerical Mathematics, Zuse Institute Berlin, 14195 Berlin, Germany; Department of Mathematics and Informatics, Freie Universität Berlin, 14195 Berlin, Germany., Daumann IM; Division of Neurobiology, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany., Wolfenberg H; Division of Neurobiology, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany., Dercksen VJ; Department of Visual Data Analysis, Zuse Institute Berlin, 14195 Berlin, Germany., Kiral FR; Division of Neurobiology, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany., Weiser M; Computational Medicine and Numerical Mathematics, Zuse Institute Berlin, 14195 Berlin, Germany., Prohaska S; Department of Visual Data Analysis, Zuse Institute Berlin, 14195 Berlin, Germany., von Kleist M; Department of Mathematics and Informatics, Freie Universität Berlin, 14195 Berlin, Germany. Electronic address: vkleist@zedat.fu-berlin.de., Hiesinger PR; Division of Neurobiology, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany. Electronic address: robin.hiesinger@fu-berlin.de.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2019 Aug 19; Vol. 50 (4), pp. 447-461.e8. Date of Electronic Publication: 2019 Jul 25.
DOI:	10.1016/j.devcel.2019.06.014
Abstrakt:	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. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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