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Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring

Brain wiring is remarkably precise, yet most neurons readily form synapses with incorrect partners when given the opportunity. Dynamic axon-dendritic positioning can restrict synaptogenic encounters, but the spatiotemporal interaction kinetics and their regulation remain essentially unknown inside d...

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Autores principales: Kiral, Ferdi Ridvan, Linneweber, Gerit Arne, Mathejczyk, Thomas, Georgiev, Svilen Veselinov, Wernet, Mathias F., Hassan, Bassem A., von Kleist, Max, Hiesinger, Peter Robin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067798/
https://www.ncbi.nlm.nih.gov/pubmed/32165611
http://dx.doi.org/10.1038/s41467-020-14781-4
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author Kiral, Ferdi Ridvan
Linneweber, Gerit Arne
Mathejczyk, Thomas
Georgiev, Svilen Veselinov
Wernet, Mathias F.
Hassan, Bassem A.
von Kleist, Max
Hiesinger, Peter Robin
author_facet Kiral, Ferdi Ridvan
Linneweber, Gerit Arne
Mathejczyk, Thomas
Georgiev, Svilen Veselinov
Wernet, Mathias F.
Hassan, Bassem A.
von Kleist, Max
Hiesinger, Peter Robin
author_sort Kiral, Ferdi Ridvan
collection PubMed
description Brain wiring is remarkably precise, yet most neurons readily form synapses with incorrect partners when given the opportunity. Dynamic axon-dendritic positioning can restrict synaptogenic encounters, but the spatiotemporal interaction kinetics and their regulation remain essentially unknown inside developing brains. Here we show that the kinetics of axonal filopodia restrict synapse formation and partner choice for neurons that are not otherwise prevented from making incorrect synapses. Using 4D imaging in developing Drosophila brains, we show that filopodial kinetics are regulated by autophagy, a prevalent degradation mechanism whose role in brain development remains poorly understood. With surprising specificity, autophagosomes form in synaptogenic filopodia, followed by filopodial collapse. Altered autophagic degradation of synaptic building material quantitatively regulates synapse formation as shown by computational modeling and genetic experiments. Increased filopodial stability enables incorrect synaptic partnerships. Hence, filopodial autophagy restricts inappropriate partner choice through a process of kinetic exclusion that critically contributes to wiring specificity.
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spelling pubmed-70677982020-03-18 Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring Kiral, Ferdi Ridvan Linneweber, Gerit Arne Mathejczyk, Thomas Georgiev, Svilen Veselinov Wernet, Mathias F. Hassan, Bassem A. von Kleist, Max Hiesinger, Peter Robin Nat Commun Article Brain wiring is remarkably precise, yet most neurons readily form synapses with incorrect partners when given the opportunity. Dynamic axon-dendritic positioning can restrict synaptogenic encounters, but the spatiotemporal interaction kinetics and their regulation remain essentially unknown inside developing brains. Here we show that the kinetics of axonal filopodia restrict synapse formation and partner choice for neurons that are not otherwise prevented from making incorrect synapses. Using 4D imaging in developing Drosophila brains, we show that filopodial kinetics are regulated by autophagy, a prevalent degradation mechanism whose role in brain development remains poorly understood. With surprising specificity, autophagosomes form in synaptogenic filopodia, followed by filopodial collapse. Altered autophagic degradation of synaptic building material quantitatively regulates synapse formation as shown by computational modeling and genetic experiments. Increased filopodial stability enables incorrect synaptic partnerships. Hence, filopodial autophagy restricts inappropriate partner choice through a process of kinetic exclusion that critically contributes to wiring specificity. Nature Publishing Group UK 2020-03-12 /pmc/articles/PMC7067798/ /pubmed/32165611 http://dx.doi.org/10.1038/s41467-020-14781-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kiral, Ferdi Ridvan
Linneweber, Gerit Arne
Mathejczyk, Thomas
Georgiev, Svilen Veselinov
Wernet, Mathias F.
Hassan, Bassem A.
von Kleist, Max
Hiesinger, Peter Robin
Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring
title Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring
title_full Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring
title_fullStr Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring
title_full_unstemmed Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring
title_short Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring
title_sort autophagy-dependent filopodial kinetics restrict synaptic partner choice during drosophila brain wiring
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067798/
https://www.ncbi.nlm.nih.gov/pubmed/32165611
http://dx.doi.org/10.1038/s41467-020-14781-4
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