{"publication_status":"published","doi":"10.1126/sciadv.aea6020","file_date_updated":"2026-05-04T09:16:36Z","abstract":[{"lang":"eng","text":"Structural and functional differences between brain hemispheres are a common feature of animal nervous systems with reduced bilateral asymmetry often linked to impaired cognitive performance. How neuronal left-right asymmetry is initiated and integrated into a bilaterally symmetrical ground pattern is poorly understood. Here, we show that the directional asymmetry of a Drosophila central brain circuit originates from axonal interactions of two types of bilateral pioneer neurons. Subsequent recruitment of neighboring neurons into the asymmetric neuropil primordium results in hemisphere-specific microcircuits. Circuit lateralization requires dynamic expression of the cell adhesion molecule Fasciclin 2 to maintain structural plasticity in axonal remodeling. Reduced circuit asymmetry following cell type–specific Fasciclin 2 manipulation affects adult brain function. These results reveal an unexpected degree of developmental plasticity of late-born Drosophila neurons in the formation of a circuit node via the lateralized recruitment of symmetric circuit components."}],"article_number":"eaea6020","language":[{"iso":"eng"}],"volume":12,"title":"Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity","year":"2026","OA_type":"gold","day":"27","oa":1,"article_type":"original","article_processing_charge":"Yes","ddc":["570"],"scopus_import":"1","date_updated":"2026-05-04T09:18:06Z","publication":"Science Advances","type":"journal_article","oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Johann W.","last_name":"Markovitsch","full_name":"Markovitsch, Johann W."},{"full_name":"Mitić, Daniel","first_name":"Daniel","last_name":"Mitić"},{"last_name":"Del Pilar Jiménez García","first_name":"Alisa","full_name":"Del Pilar Jiménez García, Alisa"},{"orcid":"0009-0003-0415-7603","full_name":"Zane, Alsberga","id":"60f7509a-f652-11ea-9d86-b963d6490d7c","first_name":"Alsberga","last_name":"Zane"},{"full_name":"Kainz, Sarah","first_name":"Sarah","last_name":"Kainz"},{"full_name":"Kaur, Rashmit","first_name":"Rashmit","last_name":"Kaur"},{"first_name":"Thomas","last_name":"Hummel","full_name":"Hummel, Thomas"}],"DOAJ_listed":"1","OA_place":"publisher","acknowledgement":"We thank I. Salecker (Flybow), B. Altenhein (Fas2-Gal4Mz507), A. Nose (UAS-intra- and extra-Fas2::YFP), and C. S. Goodman (UAS-Fas2PEST+/−), as well as the Bloomington Stock Center for providing materials and fly stocks. We thank S. Waddell and the lab, especially B. Senapati, for providing the opportunity to conduct memory experiments at the CNCB, University of Oxford, and for supervision and discussions during this period. We also thank W. Kallina, S. Ilgerl, D. Bartel, A. Grimm, and A. Litin for technical support and the Hummel Lab for stimulating discussions and critical comments on the manuscript. We acknowledge the early exploratory work of A. Mattia, S. Trkulja, C. Schönherr, S. Bogner, B. Simpson, L. Tomasek, H. Roth, H. Vokač, R. Gredler, F. Kapelari, T. Kolarova, C. Ignitsch, Á. Bautista-Soldevila, and M. Kassem.\r\nThis research was funded by the University of Vienna, the Vienna Doctoral School Cognition, Behaviour and Neuroscience (uni:docs fellowship) (to J.W.M.) and by the Austrian Science Fund (FWF) (Cluster of Excellence Neuronal Circuits in Health and Disease, grant DOI 10.55776/COE16; https://www.fwf.ac.at/en/research-radar/10.55776/COE16) (to T.H.). For open access purposes, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission.","has_accepted_license":"1","file":[{"file_id":"21786","date_updated":"2026-05-04T09:16:36Z","creator":"dernst","content_type":"application/pdf","date_created":"2026-05-04T09:16:36Z","relation":"main_file","access_level":"open_access","file_size":11101140,"checksum":"3eed470fe73e53d2a8d55d6fba6934e3","success":1,"file_name":"2026_ScienceAdv_Markovitsch.pdf"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"status":"public","month":"03","publisher":"American Association for the Advancement of Science","citation":{"apa":"Markovitsch, J. W., Mitić, D., Del Pilar Jiménez García, A., Zane, A., Kainz, S., Kaur, R., &#38; Hummel, T. (2026). Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.aea6020\">https://doi.org/10.1126/sciadv.aea6020</a>","ama":"Markovitsch JW, Mitić D, Del Pilar Jiménez García A, et al. Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity. <i>Science Advances</i>. 2026;12(13). doi:<a href=\"https://doi.org/10.1126/sciadv.aea6020\">10.1126/sciadv.aea6020</a>","ieee":"J. W. Markovitsch <i>et al.</i>, “Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity,” <i>Science Advances</i>, vol. 12, no. 13. American Association for the Advancement of Science, 2026.","chicago":"Markovitsch, Johann W., Daniel Mitić, Alisa Del Pilar Jiménez García, Alsberga Zane, Sarah Kainz, Rashmit Kaur, and Thomas Hummel. “Sequential Formation of Drosophila Circuit Asymmetry via Prolonged Structural Plasticity.” <i>Science Advances</i>. American Association for the Advancement of Science, 2026. <a href=\"https://doi.org/10.1126/sciadv.aea6020\">https://doi.org/10.1126/sciadv.aea6020</a>.","mla":"Markovitsch, Johann W., et al. “Sequential Formation of Drosophila Circuit Asymmetry via Prolonged Structural Plasticity.” <i>Science Advances</i>, vol. 12, no. 13, eaea6020, American Association for the Advancement of Science, 2026, doi:<a href=\"https://doi.org/10.1126/sciadv.aea6020\">10.1126/sciadv.aea6020</a>.","short":"J.W. Markovitsch, D. Mitić, A. Del Pilar Jiménez García, A. Zane, S. Kainz, R. Kaur, T. Hummel, Science Advances 12 (2026).","ista":"Markovitsch JW, Mitić D, Del Pilar Jiménez García A, Zane A, Kainz S, Kaur R, Hummel T. 2026. Sequential formation of Drosophila circuit asymmetry via prolonged structural plasticity. Science Advances. 12(13), eaea6020."},"department":[{"_id":"MiSi"},{"_id":"GradSch"}],"date_created":"2026-04-12T22:01:48Z","intvolume":"        12","publication_identifier":{"eissn":["2375-2548"]},"issue":"13","_id":"21707","date_published":"2026-03-27T00:00:00Z","quality_controlled":"1"}