{"id":124,"date":"2022-02-06T14:50:21","date_gmt":"2022-02-06T14:50:21","guid":{"rendered":"https:\/\/robustcircuit.flygen.org\/?page_id=124"},"modified":"2025-12-13T23:30:23","modified_gmt":"2025-12-13T23:30:23","slug":"project-2","status":"publish","type":"page","link":"https:\/\/robustcircuit.flygen.org\/?page_id=124","title":{"rendered":"Project 2"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\" id=\"robustcircuit-project-2\"><em>RobustCircuit<\/em> <strong>Project 2<\/strong><\/h2>\n\n\n\n<p id=\"robustcircuit-project-2\" class=\"wp-block-paragraph\"><em>Funding Period 2022-2026 Project. Updates on new 2026-2030 project to follow soon!<\/em><\/p>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-8f761849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:66.66%\">\n<h3 class=\"wp-block-heading\" id=\"robust-axonal-branch-patterning-through-stochastic-filopodial-dynamics\">Robust axonal branch patterning through stochastic filopodial dynamics<\/h3>\n\n\n\n<h6 class=\"wp-block-heading\" id=\"bassem-hassan-and-robin-hiesinger\">Bassem Hassan and Robin Hiesinger<\/h6>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:33.33%\">\n<div class=\"wp-block-columns alignfull is-layout-flex wp-container-core-columns-is-layout-8f761849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"is-style-rounded wp-block-image size-full is-resized\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" width=\"202\" height=\"280\" src=\"https:\/\/i0.wp.com\/robustcircuit.flygen.org\/wp-content\/uploads\/2022\/02\/BassemHassan.jpg?resize=202%2C280&#038;ssl=1\" alt=\"\" class=\"wp-image-104\" style=\"width:92px;height:auto\"\/><\/figure>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"is-style-rounded wp-block-image size-full is-resized\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" width=\"202\" height=\"285\" src=\"https:\/\/i0.wp.com\/robustcircuit.flygen.org\/wp-content\/uploads\/2022\/02\/RobinHiesinger2-1.jpg?resize=202%2C285&#038;ssl=1\" alt=\"\" class=\"wp-image-101\" style=\"aspect-ratio:0.7062937062937062;width:90px;height:auto\"\/><\/figure>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"project-2-focuses-on-axon-selection-and-branch-patterning-processes-that-are-robust-to-variable-dorsal-cluster-neuron-numbers-and-depend-on-probabilistic-filopodial-dynamics\">Project 2 focuses on axon selection and branch patterning processes that are robust to variable Dorsal Cluster Neuron numbers and depend on probabilistic filopodial dynamics.<\/h4>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Imprecision: A variable number of 10-16 axons from 22-68 Dorsal Cluster Neurons create a \u2018ladder-like\u2019 innervation pattern in the proximal medulla of the <em>Drosophila<\/em> optic lobe.&nbsp; Filopodial dynamics are stochastic and non-predictive for axon selection and branch stabilization.<\/p>\n<\/blockquote>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Robustness: The mature pattern is \u2018stereotypic\u2019 at the level of the population, i.e. appears to be highly similar in several parameters of the pattern, including relative axon positioning, branch angles and spacing.<\/p>\n<\/blockquote>\n\n\n\n<p class=\"wp-block-paragraph\">Hypothesis: Notch-dependent competition occurs within axon bundles irrespective of neuronal identity, while EGFR-dependent competition results from feedback during synapse formation.&nbsp; The robustness of both processes requires stochastic filopodial dynamics.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"project-summary\">Project Summary<\/h4>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"alignleft size-full is-resized\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" width=\"500\" height=\"500\" src=\"https:\/\/i0.wp.com\/robustcircuit.flygen.org\/wp-content\/uploads\/2022\/02\/P2-1.jpg?resize=500%2C500&#038;ssl=1\" alt=\"\" class=\"wp-image-153\" style=\"width:375px;height:375px\" srcset=\"https:\/\/i0.wp.com\/robustcircuit.flygen.org\/wp-content\/uploads\/2022\/02\/P2-1.jpg?w=500&amp;ssl=1 500w, https:\/\/i0.wp.com\/robustcircuit.flygen.org\/wp-content\/uploads\/2022\/02\/P2-1.jpg?resize=300%2C300&amp;ssl=1 300w, https:\/\/i0.wp.com\/robustcircuit.flygen.org\/wp-content\/uploads\/2022\/02\/P2-1.jpg?resize=150%2C150&amp;ssl=1 150w\" sizes=\"auto, (max-width: 500px) 100vw, 500px\" \/><figcaption class=\"wp-element-caption\">Left\/right variability of Dorsal Cluster Neuron axonal branches<\/figcaption><\/figure>\n<\/div>\n\n\n<p class=\"wp-block-paragraph\">Brain wiring relies on specific axo-dendritic patterns, yet many aspects of these patterns differ between individuals.&nbsp; Dorsal Cluster Neurons (DCNs) are contralaterally projecting neurons in both brain hemispheres that exhibit a stereotypic projection pattern of known functional importance, as recently characterized by a team of <em>RobustCircuit<\/em> PIs.&nbsp; We call this pattern stereotypic, because relative axon and branch spacing and ratios are reproducible, while individual axon position and axonal branching positions and angles are more variable.&nbsp; Remarkably, this axonal projection pattern is robust to stochastic variations in the number of neurons on both sides of the brain.&nbsp; How does the developmental process ensure a stereotyped axonal targeting and branching pattern independently of the highly imprecise number of neurons that provide the axons and branches?&nbsp; We hypothesize a sequence of two competitive selection processes based randomly exploring filopodia.&nbsp; First, axon selection occurs based on Notch signaling-dependent axonal competition; second, axonal branch patterning occurs based on an EGFR signaling-dependent feedback mechanism between synapse formation and branch stabilization.&nbsp; Both mechanisms require stochastic dynamics to generate a pool of variability for competitive selection.&nbsp; The outcome ensures robust patterns of innervation on the left and right side of the brain that are both independent of each other and which are robust to stochastic variations in neuron numbers on each side of the brain.&nbsp; The approach of <strong>P2<\/strong> is a quantitative investigation of axon and branch dynamics and outcome robustness based on advanced multi-photon <em>intravital<\/em> and <em>ex vivo<\/em> imaging techniques that have been established for DCNs in preparation for <em>RobustCircuit<\/em>.&nbsp; When these studies are concluded, we will have established a complete 4D dynamics profile and mechanistic basis for the development of a robust axonal targeting and branching pattern based on stochastic dynamics in an intact brain.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\" id=\"references\">References<\/h4>\n\n\n\n<ol class=\"wp-block-list\">\n<li class=\"\"><a href=\"http:\/\/flygen.org\/pdfs\/currbiol.2023.EGFR-autophagy.pdf\" target=\"_blank\" rel=\"noreferrer noopener\">Dutta, S.B., Linneweber, G.A., Andriatsilavo, M., <strong>Hiesinger, P.R<\/strong>.*, and <strong>Hassan, B.A.*<\/strong> (2023). EGFR-dependent suppression of synaptic autophagy is required for neuronal circuit development. <strong>Curr. Biol.,<\/strong> 33, 1-16. * co-corresponding authors.<\/a><\/li>\n\n\n\n<li class=\"\"><a href=\"http:\/\/flygen.org\/pdfs\/cellrep.2021.temperature-paper.pdf\" target=\"_blank\" rel=\"noreferrer noopener\">Kiral, F.R., Dutta, S.B., Linneweber, G.A., Poppa, C., Duch, C., von KLeist, M., <strong>Hassan, B.A.<\/strong>, and <strong>Hiesinger, P.R.<\/strong> (2021). Brain Connectivity inversely scales with developmental temperature in <em>Drosophila<\/em>, <strong>Cell Rep.<\/strong> <em>37(12):110145<\/em>.<\/a><\/li>\n\n\n\n<li class=\"\">Kessissoglou I.A., Langui D., Hasan A., Maral M., Dutta S.B., <strong>Hiesinger P.R.<\/strong>, <strong>Hassan B.A.<\/strong> <em>(2020)<\/em>. The Drosophila amyloid precursor protein homologue mediates neuronal survival and neuroglial interactions. <strong><em>PloS Biology<\/em><\/strong>, 18(12):e3000703.<\/li>\n\n\n\n<li class=\"\">Kiral, F.R., Linneweber, G.A., Mathejczyk, T., Georgiev, S.V., Wernet, M.F., <strong>Hassan, B.A.,<\/strong> von Kleist, M., <strong>Hiesinger, P.R. <\/strong><em>(2020)<\/em>. Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring. <strong><em>Nat Commun <\/em><\/strong>11(1):1325. doi: 10.1038\/s41467-020-14781-4.<\/li>\n\n\n\n<li class=\"\">Linneweber, G.A., Andriatsilavo, M., Dutta, S., Hellbruegge, L., Liu, G., Ejsmont, R,K., Fenk, L.M., Straw, A.D., Wernet, M., <strong>Hiesinger, P.R., Hassan, B.A<\/strong>. <em>(2020)<\/em>. A neurodevelopmental origin of behavioral individuality in the <em>Drosophila<\/em> visual system. <strong><em>Science <\/em><\/strong>367(6482):1112-1119. doi: 10.1126\/science.aaw7182.<\/li>\n\n\n\n<li class=\"\"><strong>Hiesinger, P.R.<\/strong> and <strong>Hassan, B.A.<\/strong> <em>(2018)<\/em>. The Evolution of Variability and Robustness in Neural Development. <strong><em>Trends in Neuroscience<\/em><\/strong> <em>41(9):577-586<\/em><\/li>\n\n\n\n<li class=\"\">Ozel, M.N., Langen, M., <strong>Hassan, B.A.<\/strong> and <strong>Hiesinger, P.R.<\/strong> <em>(2015)<\/em> Filopodial Dynamics and Growth Cone Stabilization in Drosophila Visual Circuit Development. <strong><em>eLife<\/em><\/strong>, <em>e10721<\/em><\/li>\n\n\n\n<li class=\"\"><strong>Hassan, B.A.<\/strong> and <strong>Hiesinger, P.R.<\/strong> <em>(2015)<\/em> Beyond Molecular Codes: Simple Rules to Wire Complex Brain. <strong><em>Cell<\/em><\/strong>, <em>163(2):285-291<\/em><\/li>\n<\/ol>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n","protected":false},"excerpt":{"rendered":"<p>RobustCircuit Project 2 Funding Period 2022-2026 Project. Updates on new 2026-2030 project to follow soon! Robust axonal branch patterning through stochastic filopodial dynamics Bassem Hassan and Robin Hiesinger Project 2&hellip;<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"nf_dc_page":"","footnotes":""},"class_list":["post-124","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Project 2 - RobustCircuit<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/robustcircuit.flygen.org\/?page_id=124\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Project 2 - RobustCircuit\" \/>\n<meta property=\"og:description\" content=\"RobustCircuit Project 2 Funding Period 2022-2026 Project. 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