--- _id: '10402' abstract: - lang: eng text: Branching morphogenesis governs the formation of many organs such as lung, kidney, and the neurovascular system. Many studies have explored system-specific molecular and cellular regulatory mechanisms, as well as self-organizing rules underlying branching morphogenesis. However, in addition to local cues, branched tissue growth can also be influenced by global guidance. Here, we develop a theoretical framework for a stochastic self-organized branching process in the presence of external cues. Combining analytical theory with numerical simulations, we predict differential signatures of global vs. local regulatory mechanisms on the branching pattern, such as angle distributions, domain size, and space-filling efficiency. We find that branch alignment follows a generic scaling law determined by the strength of global guidance, while local interactions influence the tissue density but not its overall territory. Finally, using zebrafish innervation as a model system, we test these key features of the model experimentally. Our work thus provides quantitative predictions to disentangle the role of different types of cues in shaping branched structures across scales. acknowledgement: We thank all members of our respective groups for helpful discussion on the paper. The authors are also grateful to Prof. Abdel El. Manira for support and sharing Tg(HUC:Gal4;UAS:Synaptohysin-GFP), to Haohao Wu for discussion, and thank Elena Zabalueva for the zebrafish schematic. The authors also acknowledge Zebrafish core facility, Genome Engineering Zebrafish and Biomedicum Imaging Core from the Karolinska Institutet for technical support. This work received funding from the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 851288 to E.H.) and under the Marie Skłodowska-Curie grant agreement No. 754411 (to M.C.U.); Swedish Research Council (to F.L., I.A. and S.H.); Knut and Alice Wallenberg Foundation (F.L. and I.A.); Swedish Brain Foundation (F.L. and S.H.); Ming Wai Lau Foundation (to F.L.); StratRegen (to F.L.); ERC Consolidator grant STEMMING-FROM-NERVE and ERC Synergy Grant KILL-OR-DIFFERENTIATE (to I.A.); Bertil Hallsten Research Foundation (to I.A.); Cancerfonden (to I.A.); the Paradifference Foundation (to I.A.); Austrian Science Fund (to I.A.); and StratNeuro (to S.H.). article_number: '6830' article_processing_charge: No article_type: original author: - first_name: Mehmet C full_name: Ucar, Mehmet C id: 50B2A802-6007-11E9-A42B-EB23E6697425 last_name: Ucar orcid: 0000-0003-0506-4217 - first_name: Dmitrii full_name: Kamenev, Dmitrii last_name: Kamenev - first_name: Kazunori full_name: Sunadome, Kazunori last_name: Sunadome - first_name: Dominik C full_name: Fachet, Dominik C id: 14FDD550-AA41-11E9-A0E5-1ACCE5697425 last_name: Fachet - first_name: Francois full_name: Lallemend, Francois last_name: Lallemend - first_name: Igor full_name: Adameyko, Igor last_name: Adameyko - first_name: Saida full_name: Hadjab, Saida last_name: Hadjab - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 citation: ama: Ucar MC, Kamenev D, Sunadome K, et al. Theory of branching morphogenesis by local interactions and global guidance. Nature Communications. 2021;12. doi:10.1038/s41467-021-27135-5 apa: Ucar, M. C., Kamenev, D., Sunadome, K., Fachet, D. C., Lallemend, F., Adameyko, I., … Hannezo, E. B. (2021). Theory of branching morphogenesis by local interactions and global guidance. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-27135-5 chicago: Ucar, Mehmet C, Dmitrii Kamenev, Kazunori Sunadome, Dominik C Fachet, Francois Lallemend, Igor Adameyko, Saida Hadjab, and Edouard B Hannezo. “Theory of Branching Morphogenesis by Local Interactions and Global Guidance.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-27135-5. ieee: M. C. Ucar et al., “Theory of branching morphogenesis by local interactions and global guidance,” Nature Communications, vol. 12. Springer Nature, 2021. ista: Ucar MC, Kamenev D, Sunadome K, Fachet DC, Lallemend F, Adameyko I, Hadjab S, Hannezo EB. 2021. Theory of branching morphogenesis by local interactions and global guidance. Nature Communications. 12, 6830. mla: Ucar, Mehmet C., et al. “Theory of Branching Morphogenesis by Local Interactions and Global Guidance.” Nature Communications, vol. 12, 6830, Springer Nature, 2021, doi:10.1038/s41467-021-27135-5. short: M.C. Ucar, D. Kamenev, K. Sunadome, D.C. Fachet, F. Lallemend, I. Adameyko, S. Hadjab, E.B. Hannezo, Nature Communications 12 (2021). date_created: 2021-12-05T23:01:40Z date_published: 2021-11-24T00:00:00Z date_updated: 2023-08-14T13:18:46Z day: '24' ddc: - '573' department: - _id: EdHa doi: 10.1038/s41467-021-27135-5 ec_funded: 1 external_id: isi: - '000722322900020' pmid: - '34819507' file: - access_level: open_access checksum: 63c56ec75314a71e63e7dd2920b3c5b5 content_type: application/pdf creator: cchlebak date_created: 2021-12-10T08:54:09Z date_updated: 2021-12-10T08:54:09Z file_id: '10529' file_name: 2021_NatComm_Ucar.pdf file_size: 2303405 relation: main_file success: 1 file_date_updated: 2021-12-10T08:54:09Z has_accepted_license: '1' intvolume: ' 12' isi: 1 language: - iso: eng month: '11' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '13058' relation: research_data status: public scopus_import: '1' status: public title: Theory of branching morphogenesis by local interactions and global guidance tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ...