{"publication":"Nature Communications","publisher":"Springer Nature","external_id":{"isi":["001075884500007"],"pmid":["37735168"]},"month":"09","date_created":"2023-10-01T22:01:13Z","publication_status":"published","_id":"14378","file":[{"relation":"main_file","file_id":"14384","content_type":"application/pdf","checksum":"4fe5423403f2531753bcd9e0fea48e05","file_name":"2023_NatureComm_Ucar.pdf","date_created":"2023-10-03T07:46:36Z","file_size":8143264,"access_level":"open_access","creator":"dernst","date_updated":"2023-10-03T07:46:36Z","success":1}],"status":"public","article_type":"original","oa_version":"Published Version","department":[{"_id":"EdHa"}],"doi":"10.1038/s41467-023-41456-7","project":[{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020","grant_number":"851288"},{"name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","date_updated":"2023-12-13T12:31:05Z","file_date_updated":"2023-10-03T07:46:36Z","acknowledgement":"We thank Dr. Kari Alitalo (University of Helsinki and Wihuri Research Institute) for critical reading of the manuscript, providing Vegfc+/− and Clp24ΔEC mouse strains and for hosting K.V.’s Academy of Finland postdoctoral researcher period (2015–2018). We thank Dr. Sara Wickström (University of Helsinki and Wihuri Research Institute) for providing Sox9:Egfp mouse\r\nstrain and the discussions. We thank Maija Atuegwu and Tapio Tainola for technical assistance. This work received funding from the Academy of Finland (K.V., 315710), Sigrid Juselius Foundation (K.V.), University of Helsinki (K.V.), Wihuri Research Institute (K.V.), the ERC under the European Union’s Horizon 2020 research and innovation program (grant agreement\r\nNo. 851288 to E.H.) and under the Marie Skłodowska-Curie grant agreement No. 754411 (to M.C.U.). Part of the work was carried out with the support of HiLIFE Laboratory Animal Centre Core Facility, University of Helsinki, Finland. Imaging was performed at the Biomedicum Imaging Unit, Helsinki University, Helsinki, Finland, with the support of Biocenter Finland. The AAVpreparations were produced at the Helsinki Virus (HelVi) Core.","ec_funded":1,"language":[{"iso":"eng"}],"day":"21","author":[{"first_name":"Mehmet C","last_name":"Ucar","orcid":"0000-0003-0506-4217","full_name":"Ucar, Mehmet C","id":"50B2A802-6007-11E9-A42B-EB23E6697425"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","last_name":"Hannezo","first_name":"Edouard B"},{"full_name":"Tiilikainen, Emmi","last_name":"Tiilikainen","first_name":"Emmi"},{"full_name":"Liaqat, Inam","last_name":"Liaqat","first_name":"Inam"},{"last_name":"Jakobsson","first_name":"Emma","full_name":"Jakobsson, Emma"},{"last_name":"Nurmi","first_name":"Harri","full_name":"Nurmi, Harri"},{"first_name":"Kari","orcid":"0000-0001-7829-3518","last_name":"Vaahtomeri","full_name":"Vaahtomeri, Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"abstract":[{"lang":"eng","text":"Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.e., tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms ensuring efficient tissue coverage remain poorly understood. Here, we use the mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing, genetic perturbations, whole-organ reconstructions and theoretical modeling to show that the dermal lymphatic capillaries tile space in an optimal, space-filling manner. This coverage is achieved by two complementary mechanisms: initial tissue invasion provides a non-optimal global scaffold via self-organized branching morphogenesis, while VEGF-C dependent side-branching from existing capillaries rapidly optimizes local coverage by directionally targeting low-density regions. With these two ingredients, we show that a minimal biophysical model can reproduce quantitatively whole-network reconstructions, across development and perturbations. Our results show that lymphatic capillary networks can exploit local self-organizing mechanisms to achieve tissue-scale optimization."}],"year":"2023","isi":1,"scopus_import":"1","quality_controlled":"1","date_published":"2023-09-21T00:00:00Z","volume":14,"pmid":1,"has_accepted_license":"1","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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"article_number":"5878","article_processing_charge":"Yes","citation":{"ieee":"M. C. Ucar <i>et al.</i>, “Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks,” <i>Nature Communications</i>, vol. 14. Springer Nature, 2023.","ama":"Ucar MC, Hannezo EB, Tiilikainen E, et al. Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. <i>Nature Communications</i>. 2023;14. doi:<a href=\"https://doi.org/10.1038/s41467-023-41456-7\">10.1038/s41467-023-41456-7</a>","apa":"Ucar, M. C., Hannezo, E. B., Tiilikainen, E., Liaqat, I., Jakobsson, E., Nurmi, H., &#38; Vaahtomeri, K. (2023). Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-023-41456-7\">https://doi.org/10.1038/s41467-023-41456-7</a>","chicago":"Ucar, Mehmet C, Edouard B Hannezo, Emmi Tiilikainen, Inam Liaqat, Emma Jakobsson, Harri Nurmi, and Kari Vaahtomeri. “Self-Organized and Directed Branching Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” <i>Nature Communications</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41467-023-41456-7\">https://doi.org/10.1038/s41467-023-41456-7</a>.","short":"M.C. Ucar, E.B. Hannezo, E. Tiilikainen, I. Liaqat, E. Jakobsson, H. Nurmi, K. Vaahtomeri, Nature Communications 14 (2023).","mla":"Ucar, Mehmet C., et al. “Self-Organized and Directed Branching Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” <i>Nature Communications</i>, vol. 14, 5878, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41467-023-41456-7\">10.1038/s41467-023-41456-7</a>.","ista":"Ucar MC, Hannezo EB, Tiilikainen E, Liaqat I, Jakobsson E, Nurmi H, Vaahtomeri K. 2023. Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. Nature Communications. 14, 5878."},"title":"Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks","intvolume":"        14","ddc":["570"],"publication_identifier":{"eissn":["2041-1723"]}}