TY - GEN A1 - Özel, M. Neset A1 - Kulkarni, Abhishek A1 - Hasan, Amr A1 - Brummer, Josephine A1 - Moldenhauer, Marian A1 - Daumann, Ilsa-Maria A1 - Wolfenberg, Heike A1 - Dercksen, Vincent J. A1 - Kiral, F. Ridvan A1 - Weiser, Martin A1 - Prohaska, Steffen A1 - von Kleist, Max A1 - Hiesinger, Peter Robin T1 - Serial synapse formation through filopodial competition for synaptic seeding factors N2 - 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. T3 - ZIB-Report - 19-45 KW - filopodia KW - growth cone dynamics KW - brain wiring KW - 2-photon microscopy KW - model Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-74397 SN - 1438-0064 ER - TY - JOUR A1 - Ozel, Mehmet Neset A1 - Kulkarni, Abhishek A1 - Hasan, Amr A1 - Brummer, Josephine A1 - Moldenhauer, Marian A1 - Daumann, Ilsa-Maria A1 - Wolfenberg, Heike A1 - Dercksen, Vincent J. A1 - Kiral, Ferdi Ridvan A1 - Weiser, Martin A1 - Prohaska, Steffen A1 - von Kleist, Max A1 - Hiesinger, Peter Robin T1 - Serial synapse formation through filopodial competition for synaptic seeding factors JF - Developmental Cell N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1016/j.devcel.2019.06.014 VL - 50 IS - 4 SP - 447 EP - 461 ER - TY - GEN A1 - Lindow, Norbert A1 - Brünig, Florian A1 - Dercksen, Vincent J. A1 - Fabig, Gunar A1 - Kiewisz, Robert A1 - Redemann, Stefanie A1 - Müller-Reichert, Thomas A1 - Prohaska, Steffen T1 - Semi-automatic Stitching of Serial Section Image Stacks with Filamentous Structures N2 - In this paper, we present a software-assisted workflow for the alignment and matching of filamentous structures across a stack of 3D serial image sections. This is achieved by a combination of automatic methods, visual validation, and interactive correction. After an initial alignment, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. This is supported by a quality assessment that visualizes regions that have been already inspected and, thus, allows a trade-off between quality and manual labor. The software tool was developed in collaboration with biologists who investigate microtubule-based spindles during cell division. To quantitatively understand the structural organization of such spindles, a 3D reconstruction of the numerous microtubules is essential. Each spindle is cut into a series of semi-thick physical sections, of which electron tomograms are acquired. The sections then need to be stitched, i.e. non-rigidly aligned; and the microtubules need to be traced in each section and connected across section boundaries. Experiments led to the conclusion that automatic methods for stitching alone provide only an incomplete solution to practical analysis needs. Automatic methods may fail due to large physical distortions, a low signal-to-noise ratio of the images, or other unexpected experimental difficulties. In such situations, semi-automatic validation and correction is required to rescue as much information as possible to derive biologically meaningful results despite of some errors related to data collection. Since the correct stitching is visually not obvious due to the number of microtubules (up to 30k) and their dense spatial arrangement, these are difficult tasks. Furthermore, a naive inspection of each microtubule is too time consuming. In addition, interactive visualization is hampered by the size of the image data (up to 100 GB). Based on the requirements of our collaborators, we present a practical solution for the semi-automatic stitching of serial section image stacks with filamentous structures. T3 - ZIB-Report - 19-30 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-73739 SN - 1438-0064 ER -