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C., Baader, C., Repina, N. A., … Liberali, P. (2026). Multiscale integration of tissue and chromatin context converts cell heterogeneity into stable intestinal patterning. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2026.06.009\">https://doi.org/10.1016/j.cell.2026.06.009</a>","ieee":"C. Schwayer <i>et al.</i>, “Multiscale integration of tissue and chromatin context converts cell heterogeneity into stable intestinal patterning,” <i>Cell</i>, vol. 189, no. 17. Cell Press, p. 5266–5282.e17, 2026.","ista":"Schwayer C, Barbiero S, Brückner D, Oost KC, Baader C, Repina NA, Kim J, Diaz OE, Uccelli I, Capolupo L, Meylan LC, Kalck V, Moos F, Suppinger S, Yang Q, Schnabl J, Kilik U, Bourdon M, Camp JG, Stockinger B, Ferrari A, Bühler M, Stadler MB, Hannezo EB, Liberali P. 2026. Multiscale integration of tissue and chromatin context converts cell heterogeneity into stable intestinal patterning. Cell. 189(17), 5266–5282.e17.","chicago":"Schwayer, Cornelia, Silvia Barbiero, David Brückner, Koen C. Oost, Clara Baader, Nicole A. Repina, Jinse Kim, et al. “Multiscale Integration of Tissue and Chromatin Context Converts Cell Heterogeneity into Stable Intestinal Patterning.” <i>Cell</i>. Cell Press, 2026. <a href=\"https://doi.org/10.1016/j.cell.2026.06.009\">https://doi.org/10.1016/j.cell.2026.06.009</a>.","short":"C. Schwayer, S. Barbiero, D. Brückner, K.C. Oost, C. Baader, N.A. Repina, J. Kim, O.E. Diaz, I. Uccelli, L. Capolupo, L.C. Meylan, V. Kalck, F. Moos, S. Suppinger, Q. Yang, J. Schnabl, U. Kilik, M. Bourdon, J.G. Camp, B. Stockinger, A. Ferrari, M. Bühler, M.B. Stadler, E.B. Hannezo, P. Liberali, Cell 189 (2026) 5266–5282.e17.","ama":"Schwayer C, Barbiero S, Brückner D, et al. Multiscale integration of tissue and chromatin context converts cell heterogeneity into stable intestinal patterning. <i>Cell</i>. 2026;189(17):5266-5282.e17. doi:<a href=\"https://doi.org/10.1016/j.cell.2026.06.009\">10.1016/j.cell.2026.06.009</a>"},"abstract":[{"text":"Tissue regeneration requires de novo patterning, which has been proposed to be facilitated by cellular heterogeneity. Yet how such heterogeneities are integrated with the mechanochemical state of the tissue and stabilized at the chromatin level into stable, spatially organized fates remains poorly understood. Using in vivo mouse intestinal regeneration models and organoids, we identify a critical density regime that produces a permissive window for heterogeneity in the mechanosensor Yes-associated protein 1 (YAP1). We show that YAP1 heterogeneity is coupled to lineage-biased chromatin accessibility and is decoded through FOXA1, which integrates the permissive chromatin state to Delta-Notch supracellular feedback and lineage commitment. This circuit generates fate bistability and preserves a memory of transient YAP1 activity, thereby maintaining spatial patterning as tissues return to homeostasis after injury. Together, our findings establish a multiscale framework in which tissue-scale mechanics tune single-cell competence and, through FOXA1-mediated bistability, convert transient heterogeneity into stable and self-organized tissue architecture.","lang":"eng"}],"publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"article_processing_charge":"Yes (in subscription journal)","title":"Multiscale integration of tissue and chromatin context converts cell heterogeneity into stable intestinal patterning","acknowledgement":"We thank the Liberali group, M. Verbeek, and C. Soneson for fruitful discussions; E. Tagliavini for IT support; J. Lüthi for Fractal support; H. Köhler for FACS sorting; T.O. Buchholz for help on cell segmentation; B. Treutlein and A. Xavier da Silveira dos Santos for help with library preparation of single-cell ATAC-seq; M. Garioni for help with mouse salivary organoids; M. Kahnwald for help with human intestinal organoids; M. Lütolf, M. Nikolaev, and O. Mitrofanova for providing material and initial training for microwell experiments; J. Tchorz and V. Orsini for intestinal tissue sections of the YAP1 activator experiment in homeostasis; R. Kageyama for DLL1-Venus-T2A-mCherry mice; J.-F. Spetz for technical assistance; C. Lambert and N. Accart for help with sample preparation; Claudia Flandoli for graphic design of schemes; and Zuzana Nascakova for the graphical abstract. We thank the Foundation Hubrecht Organoid Technology (now Foundation Hubrecht Organoid Biobank, https://www.hubrechtorganoidbiobank.org/) for the duodenal organoid line used in this study (HUB-04-A2-001). We thank C.P. Heisenberg, M. Lütolf, C. Tsiairis, J. Zaugg, G. D’Angelo, L. Giorgetti, S. Arber, and the Liberali group for reading the manuscript. C.S. was supported by the European Molecular Biology Organization (Postdoctoral Fellowship ALTF 660-2020) and the Human Frontier Science Program (HFSP) LT000746/2021-L. D.B.B. was supported by the NOMIS Foundation as a NOMIS fellow, an EMBO Postdoctoral Fellowship (ALTF 343-2022), and the Austrian Academy of Sciences through an APART-MINT Fellowship. B.S. was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust (FC001159). This work received funding from ERC to E.H. (grant number 851288) and to P.L. (grant number 758617) and from SNSF (310030_208162 and SNSF ERC TMCG-3_223263).","external_id":{"pmid":["42379166"]},"_id":"22956","publisher":"Cell Press","date_updated":"2026-10-01T08:42:00Z","ddc":["570"],"scopus_import":"1","month":"08","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","dataavailabilitystatement":"All sequencing data have been deposited at the Gene Expression Omnibus (GEO) under accession number GEO: GSE283662.\r\nAnalysis of imaging and sequencing data was developed in the Liberali lab and is available at https://github.com/LiberaliLab/symmetry-breaking-2026. Detailed information on the packages used is provided in the STAR Methods section.\r\nAny additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.","project":[{"grant_number":"ALTF 343-2022","_id":"34e2a5b5-11ca-11ed-8bc3-b2265616ef0b","name":"A mechano-chemical theory for stem cell fate decisions in organoid development"},{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"}]},{"citation":{"mla":"Tong, Xin. <i>Towards a Deeper Understanding of Meroblastic Cleavage - Supplementary Movies</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22777\">10.15479/AT-ISTA-22777</a>.","apa":"Tong, X. (2026). Towards a deeper understanding of meroblastic cleavage - supplementary movies. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-22777\">https://doi.org/10.15479/AT-ISTA-22777</a>","chicago":"Tong, Xin. “Towards a Deeper Understanding of Meroblastic Cleavage - Supplementary Movies.” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-22777\">https://doi.org/10.15479/AT-ISTA-22777</a>.","short":"X. Tong, (2026).","ama":"Tong X. Towards a deeper understanding of meroblastic cleavage - supplementary movies. 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22777\">10.15479/AT-ISTA-22777</a>","ieee":"X. Tong, “Towards a deeper understanding of meroblastic cleavage - supplementary movies.” Institute of Science and Technology Austria, 2026.","ista":"Tong X. 2026. 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B","last_name":"Hannezo","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"}],"day":"28","ddc":["530"],"date_updated":"2025-09-30T10:47:36Z","publisher":"Springer Nature","_id":"19373","external_id":{"arxiv":["2403.19900"],"pmid":["40248571"],"isi":["001434072800001"]},"acknowledgement":"We thank all members of the Hannezo and Liberali groups for fruitful discussions, as well as C. Schwayer, G. Quintas, L. Capolupo, D. Bruckner and D. Pinheiro for reading the manuscript. We also thank Y. Wu and X. Wu from the Yang group for performing experiments in the last rounds of revision and the So group at the National Institute of Biological Sciences, Beijing, for helping with the light-sheet time-lapse experiments. This work received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme via grant agreement no. 758617 (to P.L.), Swiss National Foundation (SNF) (no. POOP3_157531 to P.L.), the ERC under the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 851288 (to E.H.) and the Austrian Science Fund (FWF) (no. P 31639 to E.H.). This work was supported by the National Natural Science Foundation of China via grant no.3247060387 (to Q.Y.) and the Strategic Priority Research Program of the Chinese Academy of Sciences (no. XDB0820000 to Q.Y.) . Open access funding provided by Institute of Science and Technology (IST Austria).","title":"Mechanochemical bistability of intestinal organoids enables robust morphogenesis","article_processing_charge":"Yes (via OA deal)","publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"abstract":[{"text":"Reproducible pattern and form generation during embryogenesis is poorly understood. Intestinal organoid morphogenesis involves a number of mechanochemical regulators such as cell-type-specific cytoskeletal forces and osmotically driven lumen volume changes. It is unclear how these forces are coordinated in time and space to ensure robust morphogenesis. Here we show how mechanosensitive feedback on cytoskeletal tension gives rise to morphological bistability in a minimal model of organoid morphogenesis. In the model, lumen volume changes can impact the epithelial shape via both direct mechanical and indirect mechanosensitive mechanisms. We find that both bulged and budded crypt states are possible and dependent on the history of volume changes. We test key modelling assumptions via biophysical and pharmacological experiments to demonstrate how bistability can explain experimental observations, such as the importance of the timing of lumen shrinkage and robustness of the final morphogenetic state to mechanical perturbations. This suggests that bistability arising from feedback between cellular tensions and fluid pressure could be a general mechanism that coordinates multicellular shape changes in developing systems.","lang":"eng"}],"file_date_updated":"2025-08-05T12:12:03Z","doi":"10.1038/s41567-025-02792-1","citation":{"mla":"Xue, Shi-lei, et al. “Mechanochemical Bistability of Intestinal Organoids Enables Robust Morphogenesis.” <i>Nature Physics</i>, vol. 21, 078104, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41567-025-02792-1\">10.1038/s41567-025-02792-1</a>.","apa":"Xue, S., Yang, Q., Liberali, P., &#38; Hannezo, E. B. (2025). Mechanochemical bistability of intestinal organoids enables robust morphogenesis. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-025-02792-1\">https://doi.org/10.1038/s41567-025-02792-1</a>","short":"S. Xue, Q. Yang, P. Liberali, E.B. Hannezo, Nature Physics 21 (2025).","chicago":"Xue, Shi-lei, Qiutan Yang, Prisca Liberali, and Edouard B Hannezo. “Mechanochemical Bistability of Intestinal Organoids Enables Robust Morphogenesis.” <i>Nature Physics</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41567-025-02792-1\">https://doi.org/10.1038/s41567-025-02792-1</a>.","ama":"Xue S, Yang Q, Liberali P, Hannezo EB. Mechanochemical bistability of intestinal organoids enables robust morphogenesis. <i>Nature Physics</i>. 2025;21. doi:<a href=\"https://doi.org/10.1038/s41567-025-02792-1\">10.1038/s41567-025-02792-1</a>","ieee":"S. Xue, Q. Yang, P. Liberali, and E. B. Hannezo, “Mechanochemical bistability of intestinal organoids enables robust morphogenesis,” <i>Nature Physics</i>, vol. 21. Springer Nature, 2025.","ista":"Xue S, Yang Q, Liberali P, Hannezo EB. 2025. Mechanochemical bistability of intestinal organoids enables robust morphogenesis. Nature Physics. 21, 078104."},"corr_author":"1","department":[{"_id":"EdHa"}],"has_accepted_license":"1","project":[{"call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288"},{"grant_number":"P31639","call_identifier":"FWF","name":"Active mechano-chemical description of the cell cytoskeleton","_id":"268294B6-B435-11E9-9278-68D0E5697425"}],"article_number":"078104","oa_version":"Published Version","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"month":"02","scopus_import":"1"},{"date_published":"2025-08-26T00:00:00Z","oa":1,"date_created":"2025-09-07T22:01:32Z","type":"journal_article","issue":"34","PlanS_conform":"1","status":"public","year":"2025","intvolume":"       122","related_material":{"link":[{"url":"https://github.com/mehmetcanucar/Self-generated-chemotaxis","relation":"software"}]},"tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Proceedings of the National Academy of Sciences","fulldoi":"https://doi.org/10.1073/pnas.2504064122","publication_status":"published","volume":122,"file":[{"file_size":16069140,"creator":"dernst","file_id":"20307","content_type":"application/pdf","success":1,"relation":"main_file","date_updated":"2025-09-08T07:23:29Z","checksum":"b36abd92673b6d76376fc9434bad52cc","date_created":"2025-09-08T07:23:29Z","access_level":"open_access","file_name":"2025_PNAS_Ucar.pdf"}],"quality_controlled":"1","pmid":1,"OA_type":"hybrid","article_type":"original","day":"26","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"NanoFab"}],"isi":1,"author":[{"id":"50B2A802-6007-11E9-A42B-EB23E6697425","last_name":"Ucar","orcid":"0000-0003-0506-4217","full_name":"Ucar, Mehmet C","first_name":"Mehmet C"},{"orcid":"0009-0003-0415-7603","id":"60f7509a-f652-11ea-9d86-b963d6490d7c","last_name":"Zane","full_name":"Zane, Alsberga","first_name":"Alsberga"},{"first_name":"Jonna H","full_name":"Alanko, Jonna H","orcid":"0000-0002-7698-3061","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","last_name":"Alanko"},{"last_name":"Sixt","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","first_name":"Michael K"},{"last_name":"Hannezo","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","full_name":"Hannezo, Edouard B"}],"OA_place":"publisher","ec_funded":1,"title":"Self-generated chemotaxis of mixed cell populations","external_id":{"isi":["001562181600001"],"pmid":["40838890"]},"APC_amount":"5766,07 EUR","acknowledgement":"We thank all members of the M.S. and E.H. groups for stimulating discussions.We thank the Imaging and Optics facility, the Pre-clinical and Lab Support facility of the Institute of Science and Technology Austria for their excellent support and provided resources for the experimental research. In particular, we thank Jack Merrin from the Nanofabrication facility who generated the microfabricated channel used in this study. This work received funding fromt he European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 851288 to E.H.). M.C.U.is funded by a University of Sheffield Strategic Research Fellowship in the Physics of Life and Quantitative Biology.","ddc":["570"],"date_updated":"2026-05-20T08:59:54Z","_id":"20289","publisher":"National Academy of Sciences","department":[{"_id":"EdHa"},{"_id":"MiSi"}],"has_accepted_license":"1","corr_author":"1","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"abstract":[{"text":"Cell and tissue movement in development, cancer invasion, and immune response relies on chemical or mechanical guidance cues. In many systems, this behavior is locally directed by self-generated signaling gradients rather than long-range, prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally and navigate through self-generated gradients remains largely unexplored. Here, we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous cell populations. We find that the relative chemotactic sensitivities of different cell populations control their long-time coupling and comigration dynamics, with boundary conditions such as external cell and attractant reservoirs substantially influencing the migration patterns. Our model predicts an optimal parameter regime that enables robust and colocalized migration. We test our theoretical predictions with in vitro experiments demonstrating the comigration of distinct immune cell populations, and quantitatively reproduce observed migration patterns under wild-type and perturbed conditions. Interestingly, immune cell comigration occurs close to the predicted optimal regime. Finally, we incorporate mechanical interactions into our framework, revealing a nontrivial interplay between chemotactic and mechanical nonreciprocity in driving collective migration. Together, our findings suggest that self-generated chemotaxis is a robust strategy for the navigation of mixed cell populations.","lang":"eng"}],"doi":"10.1073/pnas.2504064122","file_date_updated":"2025-09-08T07:23:29Z","citation":{"ama":"Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. Self-generated chemotaxis of mixed cell populations. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(34). doi:<a href=\"https://doi.org/10.1073/pnas.2504064122\">10.1073/pnas.2504064122</a>","chicago":"Ucar, Mehmet C, Alsberga Zane, Jonna H Alanko, Michael K Sixt, and Edouard B Hannezo. “Self-Generated Chemotaxis of Mixed Cell Populations.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2504064122\">https://doi.org/10.1073/pnas.2504064122</a>.","short":"M.C. Ucar, A. Zane, J.H. Alanko, M.K. Sixt, E.B. Hannezo, Proceedings of the National Academy of Sciences 122 (2025).","ista":"Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. 2025. Self-generated chemotaxis of mixed cell populations. Proceedings of the National Academy of Sciences. 122(34), e2504064122.","ieee":"M. C. Ucar, A. Zane, J. H. Alanko, M. K. Sixt, and E. B. Hannezo, “Self-generated chemotaxis of mixed cell populations,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 34. National Academy of Sciences, 2025.","apa":"Ucar, M. C., Zane, A., Alanko, J. H., Sixt, M. K., &#38; Hannezo, E. B. (2025). Self-generated chemotaxis of mixed cell populations. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2504064122\">https://doi.org/10.1073/pnas.2504064122</a>","mla":"Ucar, Mehmet C., et al. “Self-Generated Chemotaxis of Mixed Cell Populations.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 34, e2504064122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2504064122\">10.1073/pnas.2504064122</a>."},"article_processing_charge":"Yes (in subscription journal)","article_number":"e2504064122","project":[{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"}],"scopus_import":"1","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"08","oa_version":"Published Version"},{"ddc":["570"],"date_updated":"2026-05-20T08:52:01Z","publisher":"Springer Nature","_id":"20424","APC_amount":"7068 EUR","external_id":{"isi":["001582555200011"],"pmid":["41006218"]},"acknowledgement":"We thank Alois Schlögl, Paula Sanematsu, Susana Moreno Flores, Bernat Corominas-Murtra, Stefania Tavano, Gayathri Singharaju, and Hannezo group members for helpful discussions, the Bioimaging facility at ISTA, as well as Matthias Merkel and Lisa Manning for sharing the 3D Voronoi code. We also thank the Champalimaud animal facility, Anna Pezzarossa and the Champalimaud ABBE platform for the help with microscopy and image processing. This work was supported by EMBO (ALTF 522-2021), a Fundação para a Ciência e Tecnologia grant to A.S.D. (PTDC/MED-ONC/5553/2020), as well as the European Research Council (grant 851288 to EH). A.S.D., S.C., and R.M.S. are supported by QuantOCancer Project Horizon European Union’s Horizon 2020 program (grant agreement No 810653).","title":"Mechanical control of cell fate decisions in the skin epidermis","article_processing_charge":"Yes","DOAJ_listed":"1","publication_identifier":{"eissn":["2041-1723"]},"abstract":[{"text":"Homeostasis relies on a precise balance of fate choices between renewal and differentiation. Although progress has been done to characterize the dynamics of single-cell fate choices, their underlying mechanistic basis often remains unclear. Concentrating on skin epidermis as a paradigm for multilayered tissues with complex fate choices, we develop a 3D vertex-based model with proliferation in the basal layer, showing that mechanical competition for space naturally gives rise to homeostasis and neutral drift dynamics that are seen experimentally. We then explore the effect of introducing mechanical heterogeneities between cellular subpopulations. We uncover that relatively small tension heterogeneities, reflected by distinct morphological changes in single-cell shapes, can be sufficient to heavily tilt cellular dynamics towards exponential growth. We thus derive a master relationship between cell shape and long-term clonal dynamics, which we validated during basal cell carcinoma initiation in mouse epidermis. Altogether, we propose a theoretical framework to link mechanical forces, quantitative cellular morphologies and cellular fate outcomes in complex tissues.","lang":"eng"}],"citation":{"ista":"Sahu P, Monteiro-Ferreira S, Canato S, Soares RM, Sánchez-Danés A, Hannezo EB. 2025. Mechanical control of cell fate decisions in the skin epidermis. Nature Communications. 16, 8440.","ieee":"P. Sahu, S. Monteiro-Ferreira, S. Canato, R. M. Soares, A. Sánchez-Danés, and E. B. Hannezo, “Mechanical control of cell fate decisions in the skin epidermis,” <i>Nature Communications</i>, vol. 16. Springer Nature, 2025.","ama":"Sahu P, Monteiro-Ferreira S, Canato S, Soares RM, Sánchez-Danés A, Hannezo EB. Mechanical control of cell fate decisions in the skin epidermis. <i>Nature Communications</i>. 2025;16. doi:<a href=\"https://doi.org/10.1038/s41467-025-62882-9\">10.1038/s41467-025-62882-9</a>","short":"P. Sahu, S. Monteiro-Ferreira, S. Canato, R.M. Soares, A. Sánchez-Danés, E.B. Hannezo, Nature Communications 16 (2025).","chicago":"Sahu, Preeti, Sara Monteiro-Ferreira, Sara Canato, Raquel Maia Soares, Adriana Sánchez-Danés, and Edouard B Hannezo. “Mechanical Control of Cell Fate Decisions in the Skin Epidermis.” <i>Nature Communications</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41467-025-62882-9\">https://doi.org/10.1038/s41467-025-62882-9</a>.","apa":"Sahu, P., Monteiro-Ferreira, S., Canato, S., Soares, R. M., Sánchez-Danés, A., &#38; Hannezo, E. B. (2025). Mechanical control of cell fate decisions in the skin epidermis. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-025-62882-9\">https://doi.org/10.1038/s41467-025-62882-9</a>","mla":"Sahu, Preeti, et al. “Mechanical Control of Cell Fate Decisions in the Skin Epidermis.” <i>Nature Communications</i>, vol. 16, 8440, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41467-025-62882-9\">10.1038/s41467-025-62882-9</a>."},"file_date_updated":"2025-10-13T12:37:04Z","doi":"10.1038/s41467-025-62882-9","corr_author":"1","department":[{"_id":"EdHa"}],"has_accepted_license":"1","project":[{"grant_number":"ALTF 522-2021","name":"Biomechanics of stem cell fate determination","_id":"628f3fb1-2b32-11ec-9570-83ce778803f7"},{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020","grant_number":"851288"}],"article_number":"8440","oa_version":"Published Version","month":"09","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","year":"2025","status":"public","intvolume":"        16","type":"journal_article","date_created":"2025-10-05T22:01:34Z","date_published":"2025-09-26T00:00:00Z","oa":1,"fulldoi":"https://doi.org/10.1038/s41467-025-62882-9","publication_status":"published","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"publication":"Nature Communications","pmid":1,"article_type":"original","OA_type":"gold","file":[{"success":1,"file_id":"20464","content_type":"application/pdf","creator":"dernst","file_size":2816813,"file_name":"2025_NatureComm_Sahu.pdf","access_level":"open_access","date_created":"2025-10-13T12:37:04Z","checksum":"d1656576883b23902545328e2d640234","relation":"main_file","date_updated":"2025-10-13T12:37:04Z"}],"quality_controlled":"1","volume":16,"OA_place":"publisher","ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","isi":1,"author":[{"first_name":"Preeti","full_name":"Sahu, Preeti","last_name":"Sahu","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E"},{"last_name":"Monteiro-Ferreira","full_name":"Monteiro-Ferreira, Sara","first_name":"Sara"},{"full_name":"Canato, Sara","first_name":"Sara","last_name":"Canato"},{"last_name":"Soares","full_name":"Soares, Raquel Maia","first_name":"Raquel Maia"},{"first_name":"Adriana","full_name":"Sánchez-Danés, Adriana","last_name":"Sánchez-Danés"},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo"}],"day":"26","acknowledged_ssus":[{"_id":"Bio"}]},{"title":"Tissue active matter: Integrating mechanics and signaling into dynamical models","acknowledgement":"We thank Fridtjof Brauns, Anna Kicheva, and Carl-Philipp Heisenberg for a critical reading of the manuscript and Claudia Flandoli for the artwork in the figures. D.B.B. was supported by the NOMIS foundation as a NOMIS Fellow and by an EMBO Postdoctoral Fellowship (ALTF 343-2022). This work received funding from the European Research Council (ERC) under the European Union\\u2019s Horizon 2020 Research and Innovation Programme Grant Agreement no. 851288.","external_id":{"isi":["001456660400001"],"pmid":["38951023"]},"_id":"18960","publisher":"Cold Spring Harbor Laboratory Press","date_updated":"2026-10-01T11:03:02Z","department":[{"_id":"EdHa"}],"corr_author":"1","doi":"10.1101/cshperspect.a041653","citation":{"short":"D. Brückner, E.B. Hannezo, Cold Spring Harbor Perspectives in Biology 17 (2025).","chicago":"Brückner, David, and Edouard B Hannezo. “Tissue Active Matter: Integrating Mechanics and Signaling into Dynamical Models.” <i>Cold Spring Harbor Perspectives in Biology</i>. Cold Spring Harbor Laboratory Press, 2025. <a href=\"https://doi.org/10.1101/cshperspect.a041653\">https://doi.org/10.1101/cshperspect.a041653</a>.","ama":"Brückner D, Hannezo EB. Tissue active matter: Integrating mechanics and signaling into dynamical models. <i>Cold Spring Harbor Perspectives in Biology</i>. 2025;17(4). doi:<a href=\"https://doi.org/10.1101/cshperspect.a041653\">10.1101/cshperspect.a041653</a>","ieee":"D. Brückner and E. B. Hannezo, “Tissue active matter: Integrating mechanics and signaling into dynamical models,” <i>Cold Spring Harbor Perspectives in Biology</i>, vol. 17, no. 4. Cold Spring Harbor Laboratory Press, 2025.","ista":"Brückner D, Hannezo EB. 2025. Tissue active matter: Integrating mechanics and signaling into dynamical models. Cold Spring Harbor Perspectives in Biology. 17(4), a041653.","mla":"Brückner, David, and Edouard B. Hannezo. “Tissue Active Matter: Integrating Mechanics and Signaling into Dynamical Models.” <i>Cold Spring Harbor Perspectives in Biology</i>, vol. 17, no. 4, a041653, Cold Spring Harbor Laboratory Press, 2025, doi:<a href=\"https://doi.org/10.1101/cshperspect.a041653\">10.1101/cshperspect.a041653</a>.","apa":"Brückner, D., &#38; Hannezo, E. B. (2025). Tissue active matter: Integrating mechanics and signaling into dynamical models. <i>Cold Spring Harbor Perspectives in Biology</i>. Cold Spring Harbor Laboratory Press. <a href=\"https://doi.org/10.1101/cshperspect.a041653\">https://doi.org/10.1101/cshperspect.a041653</a>"},"abstract":[{"lang":"eng","text":"The importance of physical forces in the morphogenesis, homeostatic function, and pathological dysfunction of multicellular tissues is being increasingly characterized, both theoretically and experimentally. Analogies between biological systems and inert materials such as foams, gels, and liquid crystals have provided striking insights into the core design principles underlying multicellular organization. However, these connections can seem surprising given that a key feature of multicellular systems is their ability to constantly consume energy, providing an active origin for the forces that they produce. Key emerging questions are, therefore, to understand whether and how this activity grants tissues novel properties that do not have counterparts in classical materials, as well as their consequences for biological function. Here, we review recent discoveries at the intersection of active matter and tissue biology, with an emphasis on how modeling and experiments can be combined to understand the dynamics of multicellular systems. These approaches suggest that a number of key biological tissue-scale phenomena, such as morphogenetic shape changes, collective migration, or fate decisions, share unifying design principles that can be described by physical models of tissue active matter."}],"publication_identifier":{"issn":["1943-0264"]},"article_processing_charge":"No","article_number":"a041653","project":[{"name":"A mechano-chemical theory for stem cell fate decisions in organoid development","_id":"34e2a5b5-11ca-11ed-8bc3-b2265616ef0b","grant_number":"ALTF 343-2022"},{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"}],"scopus_import":"1","language":[{"iso":"eng"}],"month":"04","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","oa_version":"None","date_published":"2025-04-01T00:00:00Z","date_created":"2025-01-29T13:33:47Z","issue":"4","type":"journal_article","intvolume":"        17","year":"2025","status":"public","researchdata_availability":"no","publication":"Cold Spring Harbor Perspectives in Biology","publication_status":"published","fulldoi":"https://doi.org/10.1101/cshperspect.a041653","volume":17,"supplementarymaterial":"no","quality_controlled":"1","OA_type":"closed access","article_type":"original","pmid":1,"day":"01","author":[{"full_name":"Brückner, David","first_name":"David","id":"e1e86031-6537-11eb-953a-f7ab92be508d","last_name":"Brückner","orcid":"0000-0001-7205-2975"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","orcid":"0000-0001-6005-1561","first_name":"Edouard B","full_name":"Hannezo, Edouard B"}],"isi":1,"das_tickbox":"0","ec_funded":1},{"date_updated":"2026-10-05T08:56:09Z","_id":"22807","external_id":{"biorxivid":["2025.10.15.682552"]},"acknowledgement":"We are grateful to the members of the Hannezo and Heisenberg groups for discussions and technical advice. We also thank the Imaging and Optics Facility and the Lab Support Facility at ISTA for their continuous support. Y.I.L. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skodowska-Curie Grant Agreement No. 101034413. The research was supported by funding to C.-P.H. from the NOMIS Foundation (Project ID 1.844) and to E.H. from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 851288).","title":"Non-canonical cytokinesis driven by mechanical uncoupling via nematic flows and adhesion-based invagination","biorxivid":1,"article_processing_charge":"No","abstract":[{"lang":"eng","text":"Cleavage - the series of rapid cell divisions that follow fertilization - marks the onset of metazoan development and represents a deeply conserved evolutionary process. Across animals, two principal modes exist: complete (holoblastic) and incomplete (meroblastic) cleavage. While holoblastic cleavage resembles conventional cytokinesis both in vitro and in vivo, the mechanisms underlying meroblastic cleavage have remained poorly understood. Using zebrafish embryos as a model, we show that meroblastic cleavage proceeds through a distinct two-step mechanism. The process begins with the assembly and contraction of a large, arc-shaped actomyosin cable. However, this contractile event alone is insufficient to complete division. A second phase, driven by cadherin-mediated membrane adhesion, is required to invaginate the furrow ridge. Strikingly, this transition depends on mechanical uncoupling of the contractile cable from the surrounding cortex. We demonstrate that such uncoupling arises from an active nematic instability, which both enhances contractility along the cable and generates actin depletion zones that relieve lateral connections. Together, these findings reveal that meroblastic cleavage is governed not by a single actomyosin-based event but by a sequential interplay between cytoskeletal contraction and cadherin-dependent adhesion, highlighting a mechanism fundamentally distinct from canonical cytokinesis."}],"doi":"10.1101/2025.10.15.682552","citation":{"apa":"Tong, X., Li, Y. I., Schelle, J., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (n.d.). Non-canonical cytokinesis driven by mechanical uncoupling via nematic flows and adhesion-based invagination. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2025.10.15.682552\">https://doi.org/10.1101/2025.10.15.682552</a>","mla":"Tong, Xin, et al. “Non-Canonical Cytokinesis Driven by Mechanical Uncoupling via Nematic Flows and Adhesion-Based Invagination.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2025.10.15.682552\">10.1101/2025.10.15.682552</a>.","ista":"Tong X, Li YI, Schelle J, Hannezo EB, Heisenberg C-PJ. Non-canonical cytokinesis driven by mechanical uncoupling via nematic flows and adhesion-based invagination. bioRxiv, <a href=\"https://doi.org/10.1101/2025.10.15.682552\">10.1101/2025.10.15.682552</a>.","ieee":"X. Tong, Y. I. Li, J. Schelle, E. B. Hannezo, and C.-P. J. Heisenberg, “Non-canonical cytokinesis driven by mechanical uncoupling via nematic flows and adhesion-based invagination,” <i>bioRxiv</i>. .","ama":"Tong X, Li YI, Schelle J, Hannezo EB, Heisenberg C-PJ. Non-canonical cytokinesis driven by mechanical uncoupling via nematic flows and adhesion-based invagination. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2025.10.15.682552\">10.1101/2025.10.15.682552</a>","short":"X. Tong, Y.I. Li, J. Schelle, E.B. Hannezo, C.-P.J. Heisenberg, BioRxiv (n.d.).","chicago":"Tong, Xin, Yuting I Li, Joséphine Schelle, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Non-Canonical Cytokinesis Driven by Mechanical Uncoupling via Nematic Flows and Adhesion-Based Invagination.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2025.10.15.682552\">https://doi.org/10.1101/2025.10.15.682552</a>."},"corr_author":"1","department":[{"_id":"EdHa"},{"_id":"CaHe"}],"project":[{"grant_number":"101034413","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","name":"IST-BRIDGE: International postdoctoral program","call_identifier":"H2020"},{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020"},{"_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A","name":"NOMIS Fellowship Program"}],"main_file_link":[{"url":"https://doi.org/10.1101/2025.10.15.682552","open_access":"1"}],"oa_version":"Preprint","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","language":[{"iso":"eng"}],"month":"10","year":"2025","status":"public","related_material":{"record":[{"id":"22804","relation":"dissertation_contains","status":"public"}]},"type":"preprint","date_created":"2026-09-04T12:32:21Z","date_published":"2025-10-15T00:00:00Z","oa":1,"fulldoi":"https://doi.org/10.1101/2025.10.15.682552","publication_status":"draft","tmp":{"image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"publication":"bioRxiv","OA_type":"green","OA_place":"repository","ec_funded":1,"author":[{"last_name":"Tong","id":"50F65CDC-AA30-11E9-A72B-8A12E6697425","first_name":"Xin","full_name":"Tong, Xin"},{"full_name":"Li, Yuting I","first_name":"Yuting I","last_name":"Li","id":"ee7a5ca8-8b71-11ed-b662-b3341c05b7eb"},{"last_name":"Schelle","first_name":"Joséphine","full_name":"Schelle, Joséphine"},{"orcid":"0000-0001-6005-1561","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","full_name":"Hannezo, Edouard B"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J"}],"day":"15"},{"doi":"10.1016/j.devcel.2025.04.010","file_date_updated":"2025-12-29T13:45:05Z","citation":{"mla":"Mclaren, Susannah B. P., et al. “Differential Tissue Deformability Underlies Fluid Pressure-Driven Shape Divergence of the Avian Embryonic Brain and Spinal Cord.” <i>Developmental Cell</i>, vol. 60, no. 17, Cell Press, 2025, p. 2237–2247.e4, doi:<a href=\"https://doi.org/10.1016/j.devcel.2025.04.010\">10.1016/j.devcel.2025.04.010</a>.","apa":"Mclaren, S. B. P., Xue, S., Ding, S., Winkel, A. K., Baldwin, O., Dwarakacherla, S., … Xiong, F. (2025). Differential tissue deformability underlies fluid pressure-driven shape divergence of the avian embryonic brain and spinal cord. <i>Developmental Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.devcel.2025.04.010\">https://doi.org/10.1016/j.devcel.2025.04.010</a>","chicago":"Mclaren, Susannah B.P., Shi-lei Xue, Siyuan Ding, Alexander K. Winkel, Oscar Baldwin, Shreya Dwarakacherla, Kristian Franze, Edouard B Hannezo, and Fengzhu Xiong. “Differential Tissue Deformability Underlies Fluid Pressure-Driven Shape Divergence of the Avian Embryonic Brain and Spinal Cord.” <i>Developmental Cell</i>. Cell Press, 2025. <a href=\"https://doi.org/10.1016/j.devcel.2025.04.010\">https://doi.org/10.1016/j.devcel.2025.04.010</a>.","short":"S.B.P. Mclaren, S. Xue, S. Ding, A.K. Winkel, O. Baldwin, S. Dwarakacherla, K. Franze, E.B. Hannezo, F. Xiong, Developmental Cell 60 (2025) 2237–2247.e4.","ama":"Mclaren SBP, Xue S, Ding S, et al. Differential tissue deformability underlies fluid pressure-driven shape divergence of the avian embryonic brain and spinal cord. <i>Developmental Cell</i>. 2025;60(17):2237-2247.e4. doi:<a href=\"https://doi.org/10.1016/j.devcel.2025.04.010\">10.1016/j.devcel.2025.04.010</a>","ieee":"S. B. P. Mclaren <i>et al.</i>, “Differential tissue deformability underlies fluid pressure-driven shape divergence of the avian embryonic brain and spinal cord,” <i>Developmental Cell</i>, vol. 60, no. 17. Cell Press, p. 2237–2247.e4, 2025.","ista":"Mclaren SBP, Xue S, Ding S, Winkel AK, Baldwin O, Dwarakacherla S, Franze K, Hannezo EB, Xiong F. 2025. Differential tissue deformability underlies fluid pressure-driven shape divergence of the avian embryonic brain and spinal cord. Developmental Cell. 60(17), 2237–2247.e4."},"abstract":[{"lang":"eng","text":"An enlarged brain underlies the complex central nervous system of vertebrates. The dramatic expansion of the brain that diverges its shape from the spinal cord follows neural tube closure during embryonic development. Here, we show that this differential deformation is encoded by a pre-pattern of tissue material properties in chicken embryos. Using magnetic droplets and atomic force microscopy, we demonstrate that the dorsal hindbrain is more fluid than the dorsal spinal cord, resulting in a thinning versus a resisting response to increasing lumen pressure, respectively. The dorsal hindbrain exhibits reduced apical actin and a disorganized laminin matrix consistent with tissue fluidization. Blocking the activity of neural-crest-associated matrix metalloproteinases inhibits hindbrain expansion. Transplanting dorsal hindbrain cells to the spinal cord can locally create an expanded brain-like morphology in some cases. Our findings raise questions in vertebrate head evolution and suggest a general role of mechanical pre-patterning in sculpting epithelial tubes."}],"publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"article_processing_charge":"Yes (in subscription journal)","has_accepted_license":"1","department":[{"_id":"EdHa"}],"acknowledgement":"We thank A. Dimitracopoulos, K. Kawaguchi, J. Vidigueira, B. Baum, I. McLaren, D. St Johnston, and members of the Buckley, Scarpa, Steventon, Kawaguchi, and Xiong labs for technical assistance and constructive feedback. We thank Ryan Greenhalgh for methods developed to obtain fluidity values from AFM data. We thank Nicola Lawrence, Alex Sossick, and Sargon Gross-Thebing from the Gurdon Institute Imaging Facility for microscopy support. Funding: this work was supported by a Wellcome Trust/Royal Society Sir Henry Dale Fellowship (215439/Z/19/Z) and UKRI-EPSRC Frontier Research Grant (EP/X023761/1, originally selected as an ERC Starting Grant) to F.X.; an ERC Consolidator Grant (772426), ERC Synergy Grant 101118729 UNFOLD, and Alexander von Humboldt Professorship ( Alexander von Humboldt Foundation) to K.F.; and an ERC Starting Grant (851288) to E.H.","external_id":{"pmid":["40347948"],"isi":["001570502100005"]},"publisher":"Cell Press","_id":"19703","date_updated":"2026-10-20T08:25:00Z","ddc":["570"],"title":"Differential tissue deformability underlies fluid pressure-driven shape divergence of the avian embryonic brain and spinal cord","oa_version":"Published Version","scopus_import":"1","month":"09","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"project":[{"grant_number":"851288","name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020"}],"publication":"Developmental Cell","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication_status":"published","fulldoi":"https://doi.org/10.1016/j.devcel.2025.04.010","issue":"17","type":"journal_article","intvolume":"        60","PlanS_conform":"1","year":"2025","status":"public","oa":1,"date_published":"2025-09-08T00:00:00Z","date_created":"2025-05-18T22:02:50Z","page":"2237-2247.e4","ec_funded":1,"OA_place":"publisher","day":"08","author":[{"full_name":"Mclaren, Susannah B.P.","first_name":"Susannah B.P.","last_name":"Mclaren"},{"full_name":"Xue, Shi-lei","first_name":"Shi-lei","last_name":"Xue","id":"31D2C804-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Ding","full_name":"Ding, Siyuan","first_name":"Siyuan"},{"last_name":"Winkel","full_name":"Winkel, Alexander K.","first_name":"Alexander K."},{"last_name":"Baldwin","full_name":"Baldwin, Oscar","first_name":"Oscar"},{"last_name":"Dwarakacherla","first_name":"Shreya","full_name":"Dwarakacherla, Shreya"},{"last_name":"Franze","full_name":"Franze, Kristian","first_name":"Kristian"},{"first_name":"Edouard B","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","orcid":"0000-0001-6005-1561"},{"first_name":"Fengzhu","full_name":"Xiong, Fengzhu","last_name":"Xiong"}],"isi":1,"quality_controlled":"1","file":[{"access_level":"open_access","date_created":"2025-12-29T13:45:05Z","file_name":"2025_DevelopmentalCell_McLaren.pdf","checksum":"1ca6f0822c1cbd430686d5e2a4f96401","relation":"main_file","date_updated":"2025-12-29T13:45:05Z","content_type":"application/pdf","file_id":"20872","success":1,"file_size":12564806,"creator":"dernst"}],"OA_type":"hybrid","article_type":"original","pmid":1,"volume":60},{"fulldoi":"https://doi.org/10.1038/s41567-024-02532-x","publication_status":"published","publication":"Nature Physics","date_created":"2024-07-16T12:32:17Z","date_published":"2024-09-01T00:00:00Z","oa":1,"researchdata_availability":"yes","year":"2024","status":"public","related_material":{"link":[{"url":"https://ista.ac.at/en/news/a-railroad-of-cells/","relation":"press_release","description":"News on ISTA website"}]},"intvolume":"        20","type":"journal_article","isi":1,"author":[{"first_name":"Eléonore","full_name":"Vercruysse, Eléonore","last_name":"Vercruysse"},{"full_name":"Brückner, David","first_name":"David","last_name":"Brückner","orcid":"0000-0001-7205-2975","id":"e1e86031-6537-11eb-953a-f7ab92be508d"},{"last_name":"Gómez-González","first_name":"Manuel","full_name":"Gómez-González, Manuel"},{"first_name":"Alexandre","full_name":"Remson, Alexandre","last_name":"Remson"},{"last_name":"Luciano","full_name":"Luciano, Marine","first_name":"Marine"},{"first_name":"Yohalie","full_name":"Kalukula, Yohalie","last_name":"Kalukula"},{"last_name":"Rossetti","full_name":"Rossetti, Leone","first_name":"Leone"},{"last_name":"Trepat","full_name":"Trepat, Xavier","first_name":"Xavier"},{"first_name":"Edouard B","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo"},{"last_name":"Gabriele","first_name":"Sylvain","full_name":"Gabriele, Sylvain"}],"day":"01","OA_place":"repository","ec_funded":1,"page":"1492-1500","das_tickbox":"1","supplementarymaterial":"yes","volume":20,"OA_type":"green","article_type":"original","quality_controlled":"1","corr_author":"1","department":[{"_id":"EdHa"}],"article_processing_charge":"No","publication_identifier":{"eissn":["1745-2481"],"issn":["1745-2473"]},"abstract":[{"lang":"eng","text":"The directed migration of epithelial cell collectives through coordinated movements plays a crucial role in various physiological processes and is increasingly understood at the level of large confluent monolayers. However, numerous processes rely on the migration of small groups of polarized epithelial clusters in complex environments, and their responses to external geometries remain poorly understood. To address this, we cultivate primary epithelial keratocyte tissues on adhesive microstripes to create autonomous epithelial clusters with well-defined geometries. We show that their migration efficiency is strongly influenced by the contact geometry and the orientation of cell–cell contacts with respect to the direction of migration. A combination of velocity and polarity alignment with contact regulation of locomotion in an active matter model captures quantitatively the experimental data. Furthermore, we predict that this combination of rules enables efficient navigation in complex geometries, which we confirm experimentally. Altogether, our findings provide a conceptual framework for extracting the interaction rules of active systems from their interaction with physical boundaries, as well as design principles for collective navigation in complex microenvironments."}],"doi":"10.1038/s41567-024-02532-x","citation":{"ieee":"E. Vercruysse <i>et al.</i>, “Geometry-driven migration efficiency of autonomous epithelial cell clusters,” <i>Nature Physics</i>, vol. 20. Springer Nature, pp. 1492–1500, 2024.","ista":"Vercruysse E, Brückner D, Gómez-González M, Remson A, Luciano M, Kalukula Y, Rossetti L, Trepat X, Hannezo EB, Gabriele S. 2024. Geometry-driven migration efficiency of autonomous epithelial cell clusters. Nature Physics. 20, 1492–1500.","chicago":"Vercruysse, Eléonore, David Brückner, Manuel Gómez-González, Alexandre Remson, Marine Luciano, Yohalie Kalukula, Leone Rossetti, Xavier Trepat, Edouard B Hannezo, and Sylvain Gabriele. “Geometry-Driven Migration Efficiency of Autonomous Epithelial Cell Clusters.” <i>Nature Physics</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41567-024-02532-x\">https://doi.org/10.1038/s41567-024-02532-x</a>.","short":"E. Vercruysse, D. Brückner, M. Gómez-González, A. Remson, M. Luciano, Y. Kalukula, L. Rossetti, X. Trepat, E.B. Hannezo, S. Gabriele, Nature Physics 20 (2024) 1492–1500.","ama":"Vercruysse E, Brückner D, Gómez-González M, et al. Geometry-driven migration efficiency of autonomous epithelial cell clusters. <i>Nature Physics</i>. 2024;20:1492-1500. doi:<a href=\"https://doi.org/10.1038/s41567-024-02532-x\">10.1038/s41567-024-02532-x</a>","mla":"Vercruysse, Eléonore, et al. “Geometry-Driven Migration Efficiency of Autonomous Epithelial Cell Clusters.” <i>Nature Physics</i>, vol. 20, Springer Nature, 2024, pp. 1492–500, doi:<a href=\"https://doi.org/10.1038/s41567-024-02532-x\">10.1038/s41567-024-02532-x</a>.","apa":"Vercruysse, E., Brückner, D., Gómez-González, M., Remson, A., Luciano, M., Kalukula, Y., … Gabriele, S. (2024). Geometry-driven migration efficiency of autonomous epithelial cell clusters. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-024-02532-x\">https://doi.org/10.1038/s41567-024-02532-x</a>"},"title":"Geometry-driven migration efficiency of autonomous epithelial cell clusters","date_updated":"2026-10-01T11:02:43Z","publisher":"Springer Nature","_id":"17269","external_id":{"isi":["001250246200004"]},"acknowledgement":"M.L., E.V. and S.G. acknowledge funding from the European Regional Development Fund (ERDF) Prostem Research Project (No. 1510614, Wallonia DG06), the Epiforce Project of the National Fund for Scientific Research, Belgium (FRS-FNRS; Project No. T.0092.21), the Cellsqueezer Project of FRS-FNRS (Project No. J.0061.23), the Optopattern Project of FRS-FNRS (Project no. U.NO26.22) and the Interreg MAT(T)ISSE project, which is financially supported by Interreg France-Wallonie-Vlaanderen, ERDF). A.R. and M.L. are financially supported by FRS-FNRS as a research fellow (Aspirant FNRS) and Postdoctoral Researcher (Chargée de Recherches FNRS), respectively. E.V. and Y.K. are financially supported by FRS-FNRS through grants from the Fund for Research Training in Industry and Agriculture (FRIA). This project was supported by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (Grant Agreement No. 851288 to E.H.) and Marie Skłodowska-Curie Actions (Grant Agreement No. 797621 to M.G.-G.). D.B.B. was supported by the NOMIS foundation as a NOMIS fellow and by the European Molecular Biology Organization (Postdoctoral Fellowship ALTF 343-2022) and performed this work in part at the Aspen Center for Physics, which is supported by the National Science Foundation (Grant No. PHY-1607611). X.T. and M.G.-G. acknowledge support from the Government of Catalonia (Grant No. AGAUR SGR-2017-01602 and a CERCA Programme), the Spanish Ministry for Science and Innovation and ERDF (Grant No. PGC2018-099645-B-I00), the European Research Council (Grant No. Adv-883739), Fundació la Marató de TV3 (201903-30-31-32), the European Commission (Grant No. H2020-FETPROACT-01-2016-731957), La Caixa Foundation and the Biomedical Research Center Consortium in Red (Grant No. CB15/00153) at the Carlos III Health Institute, Ministry of Science and Innovation. IBEC is recipient of a Severo Ochoa Award of Excellence from the Spanish Ministry of Economy, Trade and Business.","month":"09","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.07.17.500364"}],"oa_version":"Preprint","dataavailabilitystatement":"All data are available from the corresponding authors upon request. Source data are provided with this paper.","project":[{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"},{"name":"A mechano-chemical theory for stem cell fate decisions in organoid development","_id":"34e2a5b5-11ca-11ed-8bc3-b2265616ef0b","grant_number":"ALTF 343-2022"}]},{"year":"2023","status":"public","type":"journal_article","date_created":"2023-01-12T12:09:47Z","date_published":"2023-12-02T00:00:00Z","oa":1,"fulldoi":"https://doi.org/10.1016/j.semcdb.2022.11.005","publication_status":"published","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Seminars in Cell & Developmental Biology","pmid":1,"article_type":"review","file":[{"file_name":"2023_SeminarsCellDevBiology_CorominasMurtra.pdf","access_level":"open_access","date_created":"2024-01-08T10:16:04Z","checksum":"c619887cf130f4649bf3035417186004","relation":"main_file","date_updated":"2024-01-08T10:16:04Z","success":1,"content_type":"application/pdf","file_id":"14741","creator":"dernst","file_size":1343750}],"quality_controlled":"1","volume":"150-151","ec_funded":1,"page":"58-65","isi":1,"author":[{"orcid":"0000-0001-9806-5643","last_name":"Corominas-Murtra","id":"43BE2298-F248-11E8-B48F-1D18A9856A87","full_name":"Corominas-Murtra, Bernat","first_name":"Bernat"},{"orcid":"0000-0001-6005-1561","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B","full_name":"Hannezo, Edouard B"}],"day":"02","date_updated":"2025-04-14T07:52:27Z","ddc":["570"],"publisher":"Elsevier","_id":"12162","external_id":{"pmid":["36470715"],"isi":["001053522200001"]},"acknowledgement":"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.).\r\nB. C-M wants to acknowledge the support of the field of excellence Complexity of Life, in Basic Research and Innovation of the University of Graz.","title":"Modelling the dynamics of mammalian gut homeostasis","article_processing_charge":"Yes (via OA deal)","abstract":[{"text":"Homeostatic balance in the intestinal epithelium relies on a fast cellular turnover, which is coordinated by an intricate interplay between biochemical signalling, mechanical forces and organ geometry. We review recent modelling approaches that have been developed to understand different facets of this remarkable homeostatic equilibrium. Existing models offer different, albeit complementary, perspectives on the problem. First, biomechanical models aim to explain the local and global mechanical stresses driving cell renewal as well as tissue shape maintenance. Second, compartmental models provide insights into the conditions necessary to keep a constant flow of cells with well-defined ratios of cell types, and how perturbations can lead to an unbalance of relative compartment sizes. A third family of models address, at the cellular level, the nature and regulation of stem fate choices that are necessary to fuel cellular turnover. We also review how these different approaches are starting to be integrated together across scales, to provide quantitative predictions and new conceptual frameworks to think about the dynamics of cell renewal in complex tissues.","lang":"eng"}],"publication_identifier":{"issn":["1084-9521"]},"citation":{"ista":"Corominas-Murtra B, Hannezo EB. 2023. Modelling the dynamics of mammalian gut homeostasis. Seminars in Cell &#38; Developmental Biology. 150–151, 58–65.","ieee":"B. Corominas-Murtra and E. B. Hannezo, “Modelling the dynamics of mammalian gut homeostasis,” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 150–151. Elsevier, pp. 58–65, 2023.","ama":"Corominas-Murtra B, Hannezo EB. Modelling the dynamics of mammalian gut homeostasis. <i>Seminars in Cell &#38; Developmental Biology</i>. 2023;150-151:58-65. doi:<a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">10.1016/j.semcdb.2022.11.005</a>","chicago":"Corominas-Murtra, Bernat, and Edouard B Hannezo. “Modelling the Dynamics of Mammalian Gut Homeostasis.” <i>Seminars in Cell &#38; Developmental Biology</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">https://doi.org/10.1016/j.semcdb.2022.11.005</a>.","short":"B. Corominas-Murtra, E.B. Hannezo, Seminars in Cell &#38; Developmental Biology 150–151 (2023) 58–65.","apa":"Corominas-Murtra, B., &#38; Hannezo, E. B. (2023). Modelling the dynamics of mammalian gut homeostasis. <i>Seminars in Cell &#38; Developmental Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">https://doi.org/10.1016/j.semcdb.2022.11.005</a>","mla":"Corominas-Murtra, Bernat, and Edouard B. Hannezo. “Modelling the Dynamics of Mammalian Gut Homeostasis.” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 150–151, Elsevier, 2023, pp. 58–65, doi:<a href=\"https://doi.org/10.1016/j.semcdb.2022.11.005\">10.1016/j.semcdb.2022.11.005</a>."},"doi":"10.1016/j.semcdb.2022.11.005","file_date_updated":"2024-01-08T10:16:04Z","keyword":["Cell Biology","Developmental Biology"],"corr_author":"1","department":[{"_id":"EdHa"}],"has_accepted_license":"1","project":[{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020"}],"oa_version":"Published Version","month":"12","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1"},{"tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"PRX Life","fulldoi":"https://doi.org/10.1103/prxlife.1.013001","publication_status":"published","date_published":"2023-07-20T00:00:00Z","oa":1,"date_created":"2023-09-06T08:30:59Z","type":"journal_article","issue":"1","year":"2023","status":"public","intvolume":"         1","day":"20","author":[{"full_name":"Boocock, Daniel R","first_name":"Daniel R","orcid":"0000-0002-1585-2631","last_name":"Boocock","id":"453AF628-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tsuyoshi","full_name":"Hirashima, Tsuyoshi","last_name":"Hirashima"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","first_name":"Edouard B"}],"ec_funded":1,"volume":1,"file":[{"file_name":"2023_PRXLife_Boocock.pdf","date_created":"2023-09-15T06:30:50Z","access_level":"open_access","relation":"main_file","date_updated":"2023-09-15T06:30:50Z","checksum":"f881d98c89eb9f1aa136d7b781511553","success":1,"content_type":"application/pdf","file_id":"14335","creator":"dernst","file_size":2559520}],"quality_controlled":"1","article_type":"original","department":[{"_id":"EdHa"}],"has_accepted_license":"1","corr_author":"1","abstract":[{"text":"Living tissues are characterized by an intrinsically mechanochemical interplay of active physical forces and complex biochemical signaling pathways. Either feature alone can give rise to complex emergent phenomena, for example, mechanically driven glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion instabilities. An important question is how to quantitatively assess the contribution of these different cues to the large-scale dynamics of biological materials. We address this in Madin-Darby canine kidney (MDCK) monolayers, considering both mechanochemical feedback between extracellular signal-regulated kinase (ERK) signaling activity and cellular density as well as a mechanically active tissue rheology via a self-propelled vertex model. We show that the relative strength of active migration forces to mechanochemical couplings controls a transition from a uniform active glass to periodic spatiotemporal waves. We parametrize the model from published experimental data sets on MDCK monolayers and use it to make new predictions on the correlation functions of cellular dynamics and the dynamics of topological defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers are best described by an intermediary parameter region in which both mechanochemical couplings and noisy active propulsion have a strong influence on the dynamics. Finally, we study how tissue rheology and ERK waves produce feedback on one another and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical waves at both the local and global levels.","lang":"eng"}],"publication_identifier":{"issn":["2835-8279"]},"citation":{"mla":"Boocock, Daniel R., et al. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” <i>PRX Life</i>, vol. 1, no. 1, 013001, American Physical Society, 2023, doi:<a href=\"https://doi.org/10.1103/prxlife.1.013001\">10.1103/prxlife.1.013001</a>.","apa":"Boocock, D. R., Hirashima, T., &#38; Hannezo, E. B. (2023). Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. <i>PRX Life</i>. American Physical Society. <a href=\"https://doi.org/10.1103/prxlife.1.013001\">https://doi.org/10.1103/prxlife.1.013001</a>","chicago":"Boocock, Daniel R, Tsuyoshi Hirashima, and Edouard B Hannezo. “Interplay between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.” <i>PRX Life</i>. American Physical Society, 2023. <a href=\"https://doi.org/10.1103/prxlife.1.013001\">https://doi.org/10.1103/prxlife.1.013001</a>.","short":"D.R. Boocock, T. Hirashima, E.B. Hannezo, PRX Life 1 (2023).","ama":"Boocock DR, Hirashima T, Hannezo EB. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. <i>PRX Life</i>. 2023;1(1). doi:<a href=\"https://doi.org/10.1103/prxlife.1.013001\">10.1103/prxlife.1.013001</a>","ieee":"D. R. Boocock, T. Hirashima, and E. B. Hannezo, “Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers,” <i>PRX Life</i>, vol. 1, no. 1. American Physical Society, 2023.","ista":"Boocock DR, Hirashima T, Hannezo EB. 2023. Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers. PRX Life. 1(1), 013001."},"file_date_updated":"2023-09-15T06:30:50Z","doi":"10.1103/prxlife.1.013001","article_processing_charge":"Yes","title":"Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers","acknowledgement":"We thank all members of the Hannezo group for discussions and suggestions, as well as Sound Wai Phow for technical assistance. This work received funding from the European Research Council under the EU Horizon 2020 research and innovation program Grant Agreement No. 851288 (E.H.), JSPS KAKENHI Grant No. 21H05290, and the Ministry of Education under the Research Centres of Excellence program through the MBI at NUS.","ddc":["570"],"date_updated":"2025-04-14T07:52:27Z","publisher":"American Physical Society","_id":"14277","month":"07","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","article_number":"013001","project":[{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"}]},{"article_processing_charge":"Yes","publication_identifier":{"eissn":["2041-1723"]},"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."}],"file_date_updated":"2023-10-03T07:46:36Z","doi":"10.1038/s41467-023-41456-7","citation":{"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>","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).","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.","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.","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>","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>."},"corr_author":"1","department":[{"_id":"EdHa"}],"has_accepted_license":"1","date_updated":"2025-04-14T07:43:56Z","ddc":["570"],"_id":"14378","publisher":"Springer Nature","external_id":{"isi":["001075884500007"],"pmid":["37735168"]},"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.","title":"Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks","oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"month":"09","scopus_import":"1","project":[{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"},{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"}],"article_number":"5878","fulldoi":"https://doi.org/10.1038/s41467-023-41456-7","publication_status":"published","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Nature Communications","status":"public","year":"2023","intvolume":"        14","type":"journal_article","date_created":"2023-10-01T22:01:13Z","date_published":"2023-09-21T00:00:00Z","oa":1,"ec_funded":1,"isi":1,"author":[{"first_name":"Mehmet C","full_name":"Ucar, Mehmet C","orcid":"0000-0003-0506-4217","id":"50B2A802-6007-11E9-A42B-EB23E6697425","last_name":"Ucar"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","first_name":"Edouard B"},{"first_name":"Emmi","full_name":"Tiilikainen, Emmi","last_name":"Tiilikainen"},{"last_name":"Liaqat","first_name":"Inam","full_name":"Liaqat, Inam"},{"last_name":"Jakobsson","first_name":"Emma","full_name":"Jakobsson, Emma"},{"first_name":"Harri","full_name":"Nurmi, Harri","last_name":"Nurmi"},{"orcid":"0000-0001-7829-3518","id":"368EE576-F248-11E8-B48F-1D18A9856A87","last_name":"Vaahtomeri","first_name":"Kari","full_name":"Vaahtomeri, Kari"}],"day":"21","pmid":1,"article_type":"original","file":[{"file_size":8143264,"creator":"dernst","content_type":"application/pdf","file_id":"14384","success":1,"checksum":"4fe5423403f2531753bcd9e0fea48e05","relation":"main_file","date_updated":"2023-10-03T07:46:36Z","access_level":"open_access","date_created":"2023-10-03T07:46:36Z","file_name":"2023_NatureComm_Ucar.pdf"}],"quality_controlled":"1","volume":14},{"intvolume":"        21","related_material":{"link":[{"url":"https://github.com/JulieKlepstad/LiverDevelopment","relation":"software"}]},"status":"public","year":"2023","issue":"10","type":"journal_article","date_created":"2023-10-15T22:01:10Z","oa":1,"date_published":"2023-10-04T00:00:00Z","publication_status":"published","fulldoi":"https://doi.org/10.1371/journal.pbio.3002315","publication":"PLoS Biology","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"article_type":"original","quality_controlled":"1","file":[{"success":1,"content_type":"application/pdf","file_id":"14431","creator":"dernst","file_size":6193110,"file_name":"2023_PloSBiology_Unterweger.pdf","access_level":"open_access","date_created":"2023-10-16T07:20:49Z","checksum":"40a2b11b41d70a0e5939f8a52b66e389","date_updated":"2023-10-16T07:20:49Z","relation":"main_file"}],"volume":21,"ec_funded":1,"author":[{"last_name":"Unterweger","first_name":"Iris A.","full_name":"Unterweger, Iris A."},{"last_name":"Klepstad","full_name":"Klepstad, Julie","first_name":"Julie"},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","last_name":"Hannezo"},{"first_name":"Pia R.","full_name":"Lundegaard, Pia R.","last_name":"Lundegaard"},{"full_name":"Trusina, Ala","first_name":"Ala","last_name":"Trusina"},{"first_name":"Elke A.","full_name":"Ober, Elke A.","last_name":"Ober"}],"day":"04","publisher":"Public Library of Science","_id":"14426","ddc":["570"],"date_updated":"2025-04-14T07:52:27Z","acknowledgement":"We thank the Ober group for discussion and comments on the manuscript. We are grateful to\r\nDr. F. Lemaigre for feedback on the manuscript and Dr. T. Piotrowski for invaluable support.\r\nWe thank the department of experimental medicine (AEM) in Copenhagen for expert fish\r\ncare. We gratefully acknowledge the DanStem Imaging Platform (University of Copenhagen)\r\nfor support and assistance in this work.\r\nThis work is supported by Novo Nordisk Foundation grant NNF17CC0027852 (EAO);\r\nNordisk Foundation grant NNF19OC0058327 (EAO); Novo Nordisk Foundation grant\r\nNNF17OC0031204 (PRL); https://novonordiskfonden.dk/en/; Danish National\r\nResearch Foundation grant DNRF116 (EAO and AT); https://dg.dk/en/; John and Birthe Meyer\r\nFoundation (PRL) and European Research Council (ERC) under the EU Horizon 2020 research and Innovation Programme Grant Agreement No. 851288 (EH).","title":"Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics","article_processing_charge":"No","doi":"10.1371/journal.pbio.3002315","citation":{"apa":"Unterweger, I. A., Klepstad, J., Hannezo, E. B., Lundegaard, P. R., Trusina, A., &#38; Ober, E. A. (2023). Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3002315\">https://doi.org/10.1371/journal.pbio.3002315</a>","mla":"Unterweger, Iris A., et al. “Lineage Tracing Identifies Heterogeneous Hepatoblast Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS Biology</i>, vol. 21, no. 10, e3002315, Public Library of Science, 2023, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002315\">10.1371/journal.pbio.3002315</a>.","ama":"Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA. Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. <i>PLoS Biology</i>. 2023;21(10). doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002315\">10.1371/journal.pbio.3002315</a>","chicago":"Unterweger, Iris A., Julie Klepstad, Edouard B Hannezo, Pia R. Lundegaard, Ala Trusina, and Elke A. Ober. “Lineage Tracing Identifies Heterogeneous Hepatoblast Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS Biology</i>. Public Library of Science, 2023. <a href=\"https://doi.org/10.1371/journal.pbio.3002315\">https://doi.org/10.1371/journal.pbio.3002315</a>.","short":"I.A. Unterweger, J. Klepstad, E.B. Hannezo, P.R. Lundegaard, A. Trusina, E.A. Ober, PLoS Biology 21 (2023).","ista":"Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA. 2023. Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics. PLoS Biology. 21(10), e3002315.","ieee":"I. A. Unterweger, J. Klepstad, E. B. Hannezo, P. R. Lundegaard, A. Trusina, and E. A. Ober, “Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics,” <i>PLoS Biology</i>, vol. 21, no. 10. Public Library of Science, 2023."},"file_date_updated":"2023-10-16T07:20:49Z","publication_identifier":{"eissn":["1545-7885"]},"abstract":[{"lang":"eng","text":"To meet the physiological demands of the body, organs need to establish a functional tissue architecture and adequate size as the embryo develops to adulthood. In the liver, uni- and bipotent progenitor differentiation into hepatocytes and biliary epithelial cells (BECs), and their relative proportions, comprise the functional architecture. Yet, the contribution of individual liver progenitors at the organ level to both fates, and their specific proportion, is unresolved. Combining mathematical modelling with organ-wide, multispectral FRaeppli-NLS lineage tracing in zebrafish, we demonstrate that a precise BEC-to-hepatocyte ratio is established (i) fast, (ii) solely by heterogeneous lineage decisions from uni- and bipotent progenitors, and (iii) independent of subsequent cell type–specific proliferation. Extending lineage tracing to adulthood determined that embryonic cells undergo spatially heterogeneous three-dimensional growth associated with distinct environments. Strikingly, giant clusters comprising almost half a ventral lobe suggest lobe-specific dominant-like growth behaviours. We show substantial hepatocyte polyploidy in juveniles representing another hallmark of postembryonic liver growth. Our findings uncover heterogeneous progenitor contributions to tissue architecture-defining cell type proportions and postembryonic organ growth as key mechanisms forming the adult liver."}],"has_accepted_license":"1","department":[{"_id":"EdHa"}],"project":[{"name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","grant_number":"851288"}],"article_number":"e3002315","oa_version":"Published Version","month":"10","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"scopus_import":"1"},{"title":"CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration","ddc":["570"],"date_updated":"2026-10-23T22:30:36Z","_id":"14274","publisher":"American Association for the Advancement of Science","external_id":{"pmid":["37656776"],"isi":["001062110600003"]},"acknowledgement":"We thank I. de Vries and the Scientific Service Units (Life Sciences, Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute of Science and Technology Austria for excellent support, as well as all the rotation students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis work was supported by grants from the European Research Council under the European Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20) to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U. was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411.","keyword":["General Medicine","Immunology"],"corr_author":"1","department":[{"_id":"MiSi"},{"_id":"EdHa"},{"_id":"NanoFab"}],"article_processing_charge":"No","abstract":[{"text":"Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization.","lang":"eng"}],"publication_identifier":{"issn":["2470-9468"]},"citation":{"short":"J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B. Hannezo, M.K. Sixt, Science Immunology 8 (2023).","chicago":"Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz, Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>. American Association for the Advancement of Science, 2023. <a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">https://doi.org/10.1126/sciimmunol.adc9584</a>.","ama":"Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>. 2023;8(87). doi:<a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">10.1126/sciimmunol.adc9584</a>","ieee":"J. H. Alanko <i>et al.</i>, “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration,” <i>Science Immunology</i>, vol. 8, no. 87. American Association for the Advancement of Science, 2023.","ista":"Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB, Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. 8(87), adc9584.","mla":"Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>, vol. 8, no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:<a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">10.1126/sciimmunol.adc9584</a>.","apa":"Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin, J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">https://doi.org/10.1126/sciimmunol.adc9584</a>"},"doi":"10.1126/sciimmunol.adc9584","article_number":"adc9584","project":[{"grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular Navigation Along Spatial Gradients","call_identifier":"H2020"},{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"},{"grant_number":"W01250-B20","name":"Nano-Analytics of Cellular Systems","_id":"265E2996-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"09","language":[{"iso":"eng"}],"scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1126/sciimmunol.adc9584","open_access":"1"}],"oa_version":"Published Version","date_created":"2023-09-06T08:07:51Z","date_published":"2023-09-01T00:00:00Z","oa":1,"status":"public","year":"2023","related_material":{"record":[{"status":"public","id":"14279","relation":"research_data"},{"id":"14697","relation":"dissertation_contains","status":"public"},{"status":"public","id":"19745","relation":"dissertation_contains"}]},"intvolume":"         8","type":"journal_article","issue":"87","fulldoi":"https://doi.org/10.1126/sciimmunol.adc9584","publication_status":"published","publication":"Science Immunology","volume":8,"pmid":1,"article_type":"original","quality_controlled":"1","isi":1,"author":[{"full_name":"Alanko, Jonna H","first_name":"Jonna H","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7698-3061","last_name":"Alanko"},{"first_name":"Mehmet C","full_name":"Ucar, Mehmet C","id":"50B2A802-6007-11E9-A42B-EB23E6697425","orcid":"0000-0003-0506-4217","last_name":"Ucar"},{"orcid":"0000-0002-8518-5926","id":"3795523E-F248-11E8-B48F-1D18A9856A87","last_name":"Canigova","full_name":"Canigova, Nikola","first_name":"Nikola"},{"last_name":"Stopp","id":"489E3F00-F248-11E8-B48F-1D18A9856A87","full_name":"Stopp, Julian A","first_name":"Julian A"},{"full_name":"Schwarz, Jan","first_name":"Jan","last_name":"Schwarz","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","full_name":"Merrin, Jack","first_name":"Jack"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","orcid":"0000-0001-6005-1561","first_name":"Edouard B","full_name":"Hannezo, Edouard B"},{"first_name":"Michael K","full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179"}],"day":"01","ec_funded":1},{"volume":185,"file":[{"relation":"main_file","date_updated":"2022-03-07T07:55:23Z","checksum":"ae305060e8031297771b89dae9e36a29","date_created":"2022-03-07T07:55:23Z","access_level":"open_access","file_name":"2022_Cell_Yanagida.pdf","file_size":8478995,"creator":"dernst","file_id":"10831","content_type":"application/pdf","success":1}],"quality_controlled":"1","pmid":1,"article_type":"original","day":"22","isi":1,"author":[{"full_name":"Yanagida, Ayaka","first_name":"Ayaka","last_name":"Yanagida"},{"first_name":"Elena","full_name":"Corujo-Simon, Elena","last_name":"Corujo-Simon"},{"last_name":"Revell","first_name":"Christopher K.","full_name":"Revell, Christopher K."},{"last_name":"Sahu","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E","full_name":"Sahu, Preeti","first_name":"Preeti"},{"full_name":"Stirparo, Giuliano G.","first_name":"Giuliano G.","last_name":"Stirparo"},{"first_name":"Irene M.","full_name":"Aspalter, Irene M.","last_name":"Aspalter"},{"first_name":"Alex K.","full_name":"Winkel, Alex K.","last_name":"Winkel"},{"last_name":"Peters","first_name":"Ruby","full_name":"Peters, Ruby"},{"last_name":"De Belly","full_name":"De Belly, Henry","first_name":"Henry"},{"first_name":"Davide A.D.","full_name":"Cassani, Davide A.D.","last_name":"Cassani"},{"last_name":"Achouri","first_name":"Sarra","full_name":"Achouri, Sarra"},{"last_name":"Blumenfeld","first_name":"Raphael","full_name":"Blumenfeld, Raphael"},{"last_name":"Franze","full_name":"Franze, Kristian","first_name":"Kristian"},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","orcid":"0000-0001-6005-1561"},{"last_name":"Paluch","full_name":"Paluch, Ewa K.","first_name":"Ewa K."},{"last_name":"Nichols","full_name":"Nichols, Jennifer","first_name":"Jennifer"},{"last_name":"Chalut","first_name":"Kevin J.","full_name":"Chalut, Kevin J."}],"page":"777-793.e20","ec_funded":1,"date_published":"2022-02-22T00:00:00Z","oa":1,"date_created":"2022-03-06T23:01:52Z","type":"journal_article","issue":"5","status":"public","year":"2022","intvolume":"       185","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Cell","fulldoi":"https://doi.org/10.1016/j.cell.2022.01.022","publication_status":"published","project":[{"name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","grant_number":"851288"}],"scopus_import":"1","month":"02","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"oa_version":"Published Version","title":"Cell surface fluctuations regulate early embryonic lineage sorting","external_id":{"pmid":["35196500"],"isi":["000796293700007"]},"acknowledgement":"We are grateful to H. Niwa for Dox regulatable PB vector; G. Charras for EzrinT567D cDNA; K. Jones for tdTomato ESCs, R26-Confetti ESCs, and laboratory assistance; M. Kinoshita for pPB-CAG-H2B-BFP plasmid; P. Humphreys and D. Clements for imaging support; G. Chu, P. Attlesey, and staff for animal husbandry; S. Pallett for laboratory assistance; C. Mulas for critical feedback on the project; T. Boroviak for single-cell RNA-seq; the EMBL Genomics Core Facility for sequencing; and M. Merkel for developing and sharing the original version of the 3D Voronoi code. This work was financially supported by BBSRC ( BB/Moo4023/1 and BB/T007044/1 to K.J.C. and J.N., Alert16 grant BB/R000042 to E.K.P.), Leverhulme Trust ( RPG-2014-080 to K.J.C. and J.N.), European Research Council ( 772798 -CellFateTech to K.J.C., 311637 -MorphoCorDiv and 820188 -NanoMechShape to E.K.P., Starting Grant 851288 to E.H., and 772426 -MeChemGui to K.F.), the Isaac Newton Trust (to E.K.P.), Medical Research Council UK (MRC program award MC_UU_00012/5 to E.K.P.), the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 641639 ( ITN Biopol , H.D.B. and E.K.P.), the Alexander von Humboldt Foundation (Alexander von Humboldt Professorship to K.F.), EMBO ALTF 522-2021 (to P.S.), Centre for Trophoblast Research (Next Generation fellowship to S.A.), and JSPS Overseas Research Fellowships (to A.Y.). The Wellcome-MRC Cambridge Stem Cell Institute receives core funding from Wellcome Trust ( 203151/Z/16/Z ) and MRC ( MC_PC_17230 ). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","date_updated":"2025-07-10T11:50:00Z","ddc":["570"],"_id":"10825","publisher":"Cell Press","department":[{"_id":"EdHa"}],"has_accepted_license":"1","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"abstract":[{"text":"In development, lineage segregation is coordinated in time and space. An important example is the mammalian inner cell mass, in which the primitive endoderm (PrE, founder of the yolk sac) physically segregates from the epiblast (EPI, founder of the fetus). While the molecular requirements have been well studied, the physical mechanisms determining spatial segregation between EPI and PrE remain elusive. Here, we investigate the mechanical basis of EPI and PrE sorting. We find that rather than the differences in static cell surface mechanical parameters as in classical sorting models, it is the differences in surface fluctuations that robustly ensure physical lineage sorting. These differential surface fluctuations systematically correlate with differential cellular fluidity, which we propose together constitute a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments and modeling, we identify cell surface dynamics as a key factor orchestrating the correct spatial segregation of the founder embryonic lineages.","lang":"eng"}],"citation":{"mla":"Yanagida, Ayaka, et al. “Cell Surface Fluctuations Regulate Early Embryonic Lineage Sorting.” <i>Cell</i>, vol. 185, no. 5, Cell Press, 2022, p. 777–793.e20, doi:<a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">10.1016/j.cell.2022.01.022</a>.","apa":"Yanagida, A., Corujo-Simon, E., Revell, C. K., Sahu, P., Stirparo, G. G., Aspalter, I. M., … Chalut, K. J. (2022). Cell surface fluctuations regulate early embryonic lineage sorting. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">https://doi.org/10.1016/j.cell.2022.01.022</a>","chicago":"Yanagida, Ayaka, Elena Corujo-Simon, Christopher K. Revell, Preeti Sahu, Giuliano G. Stirparo, Irene M. Aspalter, Alex K. Winkel, et al. “Cell Surface Fluctuations Regulate Early Embryonic Lineage Sorting.” <i>Cell</i>. Cell Press, 2022. <a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">https://doi.org/10.1016/j.cell.2022.01.022</a>.","short":"A. Yanagida, E. Corujo-Simon, C.K. Revell, P. Sahu, G.G. Stirparo, I.M. Aspalter, A.K. Winkel, R. Peters, H. De Belly, D.A.D. Cassani, S. Achouri, R. Blumenfeld, K. Franze, E.B. Hannezo, E.K. Paluch, J. Nichols, K.J. Chalut, Cell 185 (2022) 777–793.e20.","ama":"Yanagida A, Corujo-Simon E, Revell CK, et al. Cell surface fluctuations regulate early embryonic lineage sorting. <i>Cell</i>. 2022;185(5):777-793.e20. doi:<a href=\"https://doi.org/10.1016/j.cell.2022.01.022\">10.1016/j.cell.2022.01.022</a>","ieee":"A. Yanagida <i>et al.</i>, “Cell surface fluctuations regulate early embryonic lineage sorting,” <i>Cell</i>, vol. 185, no. 5. Cell Press, p. 777–793.e20, 2022.","ista":"Yanagida A, Corujo-Simon E, Revell CK, Sahu P, Stirparo GG, Aspalter IM, Winkel AK, Peters R, De Belly H, Cassani DAD, Achouri S, Blumenfeld R, Franze K, Hannezo EB, Paluch EK, Nichols J, Chalut KJ. 2022. Cell surface fluctuations regulate early embryonic lineage sorting. Cell. 185(5), 777–793.e20."},"file_date_updated":"2022-03-07T07:55:23Z","doi":"10.1016/j.cell.2022.01.022","article_processing_charge":"No"},{"author":[{"first_name":"Diana C","full_name":"Nunes Pinheiro, Diana C","last_name":"Nunes Pinheiro","orcid":"0000-0003-4333-7503","id":"2E839F16-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kardos, Roland","first_name":"Roland","id":"4039350E-F248-11E8-B48F-1D18A9856A87","last_name":"Kardos"},{"last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","first_name":"Edouard B","full_name":"Hannezo, Edouard B"},{"first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg"}],"isi":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"day":"01","ec_funded":1,"page":"1482-1493","volume":18,"article_type":"original","quality_controlled":"1","file":[{"checksum":"c86a8e8d80d1bfc46d56a01e88a2526a","date_updated":"2023-01-27T07:32:01Z","relation":"main_file","access_level":"open_access","date_created":"2023-01-27T07:32:01Z","file_name":"2022_NaturePhysics_Pinheiro.pdf","file_size":36703569,"creator":"dernst","content_type":"application/pdf","file_id":"12412","success":1}],"publication_status":"published","fulldoi":"https://doi.org/10.1038/s41567-022-01787-6","publication":"Nature Physics","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_created":"2023-01-16T09:45:19Z","oa":1,"date_published":"2022-12-01T00:00:00Z","intvolume":"        18","status":"public","year":"2022","issue":"12","type":"journal_article","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"12","language":[{"iso":"eng"}],"scopus_import":"1","oa_version":"Published Version","project":[{"name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation","_id":"26520D1E-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 850-2017"},{"grant_number":"ALTF 850-2017","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation","_id":"26520D1E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"},{"grant_number":"742573","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","_id":"260F1432-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"corr_author":"1","keyword":["General Physics and Astronomy"],"has_accepted_license":"1","department":[{"_id":"CaHe"},{"_id":"EdHa"}],"article_processing_charge":"No","doi":"10.1038/s41567-022-01787-6","file_date_updated":"2023-01-27T07:32:01Z","citation":{"apa":"Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-022-01787-6\">https://doi.org/10.1038/s41567-022-01787-6</a>","mla":"Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>, vol. 18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:<a href=\"https://doi.org/10.1038/s41567-022-01787-6\">10.1038/s41567-022-01787-6</a>.","ama":"Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. <i>Nature Physics</i>. 2022;18(12):1482-1493. doi:<a href=\"https://doi.org/10.1038/s41567-022-01787-6\">10.1038/s41567-022-01787-6</a>","chicago":"Nunes Pinheiro, Diana C, Roland Kardos, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41567-022-01787-6\">https://doi.org/10.1038/s41567-022-01787-6</a>.","short":"D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 18 (2022) 1482–1493.","ista":"Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. 2022. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. 18(12), 1482–1493.","ieee":"D. C. Nunes Pinheiro, R. Kardos, E. B. Hannezo, and C.-P. J. Heisenberg, “Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming,” <i>Nature Physics</i>, vol. 18, no. 12. Springer Nature, pp. 1482–1493, 2022."},"publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"abstract":[{"text":"Embryo development requires biochemical signalling to generate patterns of cell fates and active mechanical forces to drive tissue shape changes. However, how these processes are coordinated, and how tissue patterning is preserved despite the cellular flows occurring during morphogenesis, remains poorly understood. Gastrulation is a crucial embryonic stage that involves both patterning and internalization of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos, a gradient in Nodal signalling orchestrates pattern-preserving internalization movements by triggering a motility-driven unjamming transition. In addition to its role as a morphogen determining embryo patterning, graded Nodal signalling mechanically subdivides the mesendoderm into a small fraction of highly protrusive leader cells, able to autonomously internalize via local unjamming, and less protrusive followers, which need to be pulled inwards by the leaders. The Nodal gradient further enforces a code of preferential adhesion coupling leaders to their immediate followers, resulting in a collective and ordered mode of internalization that preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal signalling into minimal active particle simulations quantitatively predicts both physiological and experimentally perturbed internalization movements. This provides a quantitative framework for how a morphogen-encoded unjamming transition can bidirectionally couple tissue mechanics with patterning during complex three-dimensional morphogenesis.","lang":"eng"}],"title":"Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming","publisher":"Springer Nature","_id":"12209","ddc":["570"],"date_updated":"2025-04-14T07:46:59Z","acknowledgement":"We thank K. Sampath, A. Pauli and Y. Bellaїche for feedback on the manuscript. We also thank the members of the Heisenberg group, in particular A. Schauer and F. Nur Arslan, for help, technical advice and discussions, and the Bioimaging and Life Science facilities at IST\r\nAustria for continuous support. We thank C. Flandoli for the artwork in the figures. This work was supported by postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P. and the European Union (European Research Council starting grant 851288 to É.H. and European Research Council advanced grant 742573 to C.-P.H.).","external_id":{"isi":["000871319900002"]}},{"title":"Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids","ddc":["570"],"date_updated":"2025-06-11T13:53:55Z","_id":"12217","publisher":"Springer Nature","external_id":{"isi":["000850348400025"],"pmid":["36064947"]},"acknowledgement":"A.R.B. acknowledges the financial support of the European Research Council (ERC) through the funding of the grant Principles of Integrin Mechanics and Adhesion (PoINT) and the German Research Foundation (DFG, SFB 1032, project ID 201269156). E.H. was supported by the European Union (European Research Council Starting Grant 851288). D.S., M.R., and R.R. acknowledge the support by the German Research Foundation (DFG, SFB1321 Modeling and Targeting Pancreatic Cancer, Project S01, project ID 329628492). C.S. and M.R. acknowledge the support by the German Research Foundation (DFG, SFB1321 Modeling and Targeting Pancreatic Cancer, Project 12, project ID 329628492). M.R. was supported by the German Research Foundation (DFG RE 3723/4-1). A.P. and M.R. were supported by the German Cancer Aid (Max-Eder Program 111273 and 70114328).\r\nOpen Access funding enabled and organized by Projekt DEAL.","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"department":[{"_id":"EdHa"}],"has_accepted_license":"1","article_processing_charge":"No","abstract":[{"text":"The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.","lang":"eng"}],"publication_identifier":{"issn":["2041-1723"]},"doi":"10.1038/s41467-022-32806-y","citation":{"mla":"Randriamanantsoa, S., et al. “Spatiotemporal Dynamics of Self-Organized Branching in Pancreas-Derived Organoids.” <i>Nature Communications</i>, vol. 13, 5219, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32806-y\">10.1038/s41467-022-32806-y</a>.","apa":"Randriamanantsoa, S., Papargyriou, A., Maurer, H. C., Peschke, K., Schuster, M., Zecchin, G., … Bausch, A. R. (2022). Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32806-y\">https://doi.org/10.1038/s41467-022-32806-y</a>","chicago":"Randriamanantsoa, S., A. Papargyriou, H. C. Maurer, K. Peschke, M. Schuster, G. Zecchin, K. Steiger, et al. “Spatiotemporal Dynamics of Self-Organized Branching in Pancreas-Derived Organoids.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32806-y\">https://doi.org/10.1038/s41467-022-32806-y</a>.","short":"S. Randriamanantsoa, A. Papargyriou, H.C. Maurer, K. Peschke, M. Schuster, G. Zecchin, K. Steiger, R. Öllinger, D. Saur, C. Scheel, R. Rad, E.B. Hannezo, M. Reichert, A.R. Bausch, Nature Communications 13 (2022).","ama":"Randriamanantsoa S, Papargyriou A, Maurer HC, et al. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32806-y\">10.1038/s41467-022-32806-y</a>","ieee":"S. Randriamanantsoa <i>et al.</i>, “Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","ista":"Randriamanantsoa S, Papargyriou A, Maurer HC, Peschke K, Schuster M, Zecchin G, Steiger K, Öllinger R, Saur D, Scheel C, Rad R, Hannezo EB, Reichert M, Bausch AR. 2022. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. Nature Communications. 13, 5219."},"file_date_updated":"2023-01-27T08:14:48Z","article_number":"5219","project":[{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020","grant_number":"851288"}],"month":"09","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","oa_version":"Published Version","date_created":"2023-01-16T09:46:53Z","date_published":"2022-09-05T00:00:00Z","oa":1,"status":"public","year":"2022","related_material":{"record":[{"status":"public","relation":"research_data","id":"13068"}]},"intvolume":"        13","type":"journal_article","fulldoi":"https://doi.org/10.1038/s41467-022-32806-y","publication_status":"published","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication":"Nature Communications","volume":13,"pmid":1,"article_type":"original","file":[{"success":1,"content_type":"application/pdf","file_id":"12416","creator":"dernst","file_size":22645149,"file_name":"2022_NatureCommunications_Randriamanantsoa.pdf","date_created":"2023-01-27T08:14:48Z","access_level":"open_access","relation":"main_file","date_updated":"2023-01-27T08:14:48Z","checksum":"295261b5172274fd5b8f85a6a6058828"}],"quality_controlled":"1","isi":1,"author":[{"full_name":"Randriamanantsoa, S.","first_name":"S.","last_name":"Randriamanantsoa"},{"last_name":"Papargyriou","full_name":"Papargyriou, A.","first_name":"A."},{"first_name":"H. C.","full_name":"Maurer, H. C.","last_name":"Maurer"},{"first_name":"K.","full_name":"Peschke, K.","last_name":"Peschke"},{"first_name":"M.","full_name":"Schuster, M.","last_name":"Schuster"},{"first_name":"G.","full_name":"Zecchin, G.","last_name":"Zecchin"},{"full_name":"Steiger, K.","first_name":"K.","last_name":"Steiger"},{"first_name":"R.","full_name":"Öllinger, R.","last_name":"Öllinger"},{"last_name":"Saur","full_name":"Saur, D.","first_name":"D."},{"full_name":"Scheel, C.","first_name":"C.","last_name":"Scheel"},{"last_name":"Rad","full_name":"Rad, R.","first_name":"R."},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo"},{"full_name":"Reichert, M.","first_name":"M.","last_name":"Reichert"},{"full_name":"Bausch, A. R.","first_name":"A. R.","last_name":"Bausch"}],"day":"05","ec_funded":1},{"volume":8,"article_type":"original","pmid":1,"quality_controlled":"1","file":[{"creator":"dernst","file_size":1636732,"success":1,"file_id":"12444","content_type":"application/pdf","date_updated":"2023-01-30T09:27:49Z","relation":"main_file","checksum":"f59cdb824e5d4221045def81f46f6c65","file_name":"2022_ScienceAdvances_Stock.pdf","date_created":"2023-01-30T09:27:49Z","access_level":"open_access"}],"author":[{"first_name":"Jessica","full_name":"Stock, Jessica","last_name":"Stock"},{"last_name":"Kazmar","first_name":"Tomas","full_name":"Kazmar, Tomas"},{"last_name":"Schlumm","first_name":"Friederike","full_name":"Schlumm, Friederike"},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"last_name":"Pauli","first_name":"Andrea","full_name":"Pauli, Andrea"}],"isi":1,"day":"14","ec_funded":1,"date_created":"2023-01-16T09:57:10Z","oa":1,"date_published":"2022-09-14T00:00:00Z","intvolume":"         8","year":"2022","status":"public","issue":"37","type":"journal_article","publication_status":"published","fulldoi":"https://doi.org/10.1126/sciadv.add2488","publication":"Science Advances","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"article_number":"eadd2488","project":[{"grant_number":"851288","call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis"}],"month":"09","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","language":[{"iso":"eng"}],"scopus_import":"1","oa_version":"Published Version","title":"A self-generated Toddler gradient guides mesodermal cell migration","_id":"12253","publisher":"American Association for the Advancement of Science","ddc":["570"],"date_updated":"2025-04-14T07:52:27Z","acknowledgement":"We thank K. Aumayer and the team of the biooptics facility at the Vienna Biocenter, particularly P. Pasierbek and T. Müller, for support with microscopy; K. Panser, C. Pribitzer, and the animal facility personnel for taking care of zebrafish; M. Binner and A. Bandura for help with genotyping; M. Codina Tobias for help with establishing the conditions for the Toddler overexpression compensation experiment; T. Lubiana Alves for sharing the code for scRNA-Seq analyses; the Heisenberg laboratory, particularly D. Pinheiro, for joint laboratory meetings, discussions on the project, and providing the tg(gsc:CAAX-GFP) fish line; the Raz laboratory for providing the Lifeact-GFP plasmid; A. Andersen, A. Schier, C.-P. Heisenberg, and E. Tanaka for comments on the manuscript; and the entire Pauli laboratory, particularly K. Gert and V. Deneke, for valuable discussions and feedback on the manuscript. Funding: Work in A.P.’s laboratory has been supported by the IMP, which receives institutional funding from Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter grant FFG-852936), as well as the FWF START program (Y 1031-B28 to A.P.), the Human Frontier Science Program (HFSP) Career Development Award (CDA00066/2015 to A.P.) and Young Investigator Grant (RGY0079/2020 to A.P.), the SFB RNA-Deco (project number F 80 to A.P.), a Whitman Center Fellowship from the Marine Biological Laboratory (to A.P.), and EMBO-YIP funds (to A.P.). This work was supported by the European Union (European Research Council Starting Grant 851288 to E.H.). For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript (AAM) version arising from this submission.","external_id":{"pmid":["36103529"],"isi":["000888875000009"]},"has_accepted_license":"1","department":[{"_id":"EdHa"}],"article_processing_charge":"No","doi":"10.1126/sciadv.add2488","file_date_updated":"2023-01-30T09:27:49Z","citation":{"ama":"Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. A self-generated Toddler gradient guides mesodermal cell migration. <i>Science Advances</i>. 2022;8(37). doi:<a href=\"https://doi.org/10.1126/sciadv.add2488\">10.1126/sciadv.add2488</a>","short":"J. Stock, T. Kazmar, F. Schlumm, E.B. Hannezo, A. Pauli, Science Advances 8 (2022).","chicago":"Stock, Jessica, Tomas Kazmar, Friederike Schlumm, Edouard B Hannezo, and Andrea Pauli. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.” <i>Science Advances</i>. American Association for the Advancement of Science, 2022. <a href=\"https://doi.org/10.1126/sciadv.add2488\">https://doi.org/10.1126/sciadv.add2488</a>.","ista":"Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. 2022. A self-generated Toddler gradient guides mesodermal cell migration. Science Advances. 8(37), eadd2488.","ieee":"J. Stock, T. Kazmar, F. Schlumm, E. B. Hannezo, and A. Pauli, “A self-generated Toddler gradient guides mesodermal cell migration,” <i>Science Advances</i>, vol. 8, no. 37. American Association for the Advancement of Science, 2022.","apa":"Stock, J., Kazmar, T., Schlumm, F., Hannezo, E. B., &#38; Pauli, A. (2022). A self-generated Toddler gradient guides mesodermal cell migration. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.add2488\">https://doi.org/10.1126/sciadv.add2488</a>","mla":"Stock, Jessica, et al. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.” <i>Science Advances</i>, vol. 8, no. 37, eadd2488, American Association for the Advancement of Science, 2022, doi:<a href=\"https://doi.org/10.1126/sciadv.add2488\">10.1126/sciadv.add2488</a>."},"publication_identifier":{"issn":["2375-2548"]},"abstract":[{"text":"The sculpting of germ layers during gastrulation relies on the coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor–based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo.","lang":"eng"}]},{"scopus_import":"1","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"07","oa_version":"Submitted Version","main_file_link":[{"open_access":"1","url":"https://helda.helsinki.fi/items/94433455-4854-45c0-9de8-7326caea8780"}],"project":[{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"}],"department":[{"_id":"EdHa"}],"corr_author":"1","keyword":["Multidisciplinary"],"doi":"10.1038/s41586-022-04962-0","citation":{"mla":"Azkanaz, Maria, et al. “Retrograde Movements Determine Effective Stem Cell Numbers in the Intestine.” <i>Nature</i>, vol. 607, no. 7919, Springer Nature, 2022, pp. 548–54, doi:<a href=\"https://doi.org/10.1038/s41586-022-04962-0\">10.1038/s41586-022-04962-0</a>.","apa":"Azkanaz, M., Corominas-Murtra, B., Ellenbroek, S. I. J., Bruens, L., Webb, A. T., Laskaris, D., … van Rheenen, J. (2022). Retrograde movements determine effective stem cell numbers in the intestine. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-022-04962-0\">https://doi.org/10.1038/s41586-022-04962-0</a>","short":"M. Azkanaz, B. Corominas-Murtra, S.I.J. Ellenbroek, L. Bruens, A.T. Webb, D. Laskaris, K.C. Oost, S.J.A. Lafirenze, K. Annusver, H.A. Messal, S. Iqbal, D.J. Flanagan, D.J. Huels, F. Rojas-Rodríguez, M. Vizoso, M. Kasper, O.J. Sansom, H.J. Snippert, P. Liberali, B.D. Simons, P. Katajisto, E.B. Hannezo, J. van Rheenen, Nature 607 (2022) 548–554.","chicago":"Azkanaz, Maria, Bernat Corominas-Murtra, Saskia I. J. Ellenbroek, Lotte Bruens, Anna T. Webb, Dimitrios Laskaris, Koen C. Oost, et al. “Retrograde Movements Determine Effective Stem Cell Numbers in the Intestine.” <i>Nature</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41586-022-04962-0\">https://doi.org/10.1038/s41586-022-04962-0</a>.","ama":"Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, et al. Retrograde movements determine effective stem cell numbers in the intestine. <i>Nature</i>. 2022;607(7919):548-554. doi:<a href=\"https://doi.org/10.1038/s41586-022-04962-0\">10.1038/s41586-022-04962-0</a>","ieee":"M. Azkanaz <i>et al.</i>, “Retrograde movements determine effective stem cell numbers in the intestine,” <i>Nature</i>, vol. 607, no. 7919. Springer Nature, pp. 548–554, 2022.","ista":"Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, Bruens L, Webb AT, Laskaris D, Oost KC, Lafirenze SJA, Annusver K, Messal HA, Iqbal S, Flanagan DJ, Huels DJ, Rojas-Rodríguez F, Vizoso M, Kasper M, Sansom OJ, Snippert HJ, Liberali P, Simons BD, Katajisto P, Hannezo EB, van Rheenen J. 2022. Retrograde movements determine effective stem cell numbers in the intestine. Nature. 607(7919), 548–554."},"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"abstract":[{"lang":"eng","text":"The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts1,2,3. Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated."}],"article_processing_charge":"No","title":"Retrograde movements determine effective stem cell numbers in the intestine","acknowledgement":"We thank the members of the van Rheenen laboratory for reading the manuscript, and the members of the bioimaging, FACS and animal facility of the NKI for experimental support. We acknowledge the staff at the MedH Flow Cytometry core facility, Karolinska Institutet, and LCI facility/Nikon Center of Excellence, Karolinska Institutet. This work was financially supported by the Netherlands Organization of Scientific Research NWO (Veni grant 863.15.011 to S.I.J.E. and Vici grant 09150182110004 to J.v.R.) and the CancerGenomics.nl (Netherlands Organisation for Scientific Research) program (to J.v.R.) the Doctor Josef Steiner Foundation (to J.v.R). B.D.S. acknowledges funding from the Royal Society E.P. Abraham Research Professorship (RP\\R1\\180165) and the Wellcome Trust (098357/Z/12/Z and 219478/Z/19/Z). B.C.-M. acknowledges the support of the field of excellence ‘Complexity of life in basic research and innovation’ of the University of Graz. O.J.S. and their laboratory acknowledge CRUK core funding to the CRUK Beatson Institute (A17196 and A31287) and CRUK core funding to the Sansom laboratory (A21139). P.K. and their laboratory are supported by grants from the Swedish Research Council (2018-03078), Cancerfonden (190634), Academy of Finland Centre of Excellence (266869, 304591 and 320185) and the Jane and Aatos Erkko Foundation. P.L. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 758617). E.H. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 851288).","external_id":{"pmid":["35831497"],"isi":["000824430000004"]},"publisher":"Springer Nature","_id":"12274","date_updated":"2025-04-14T07:52:27Z","day":"13","author":[{"first_name":"Maria","full_name":"Azkanaz, Maria","last_name":"Azkanaz"},{"id":"43BE2298-F248-11E8-B48F-1D18A9856A87","last_name":"Corominas-Murtra","orcid":"0000-0001-9806-5643","full_name":"Corominas-Murtra, Bernat","first_name":"Bernat"},{"last_name":"Ellenbroek","first_name":"Saskia I. J.","full_name":"Ellenbroek, Saskia I. J."},{"full_name":"Bruens, Lotte","first_name":"Lotte","last_name":"Bruens"},{"full_name":"Webb, Anna T.","first_name":"Anna T.","last_name":"Webb"},{"full_name":"Laskaris, Dimitrios","first_name":"Dimitrios","last_name":"Laskaris"},{"full_name":"Oost, Koen C.","first_name":"Koen C.","last_name":"Oost"},{"full_name":"Lafirenze, Simona J. A.","first_name":"Simona J. A.","last_name":"Lafirenze"},{"last_name":"Annusver","first_name":"Karl","full_name":"Annusver, Karl"},{"last_name":"Messal","full_name":"Messal, Hendrik A.","first_name":"Hendrik A."},{"full_name":"Iqbal, Sharif","first_name":"Sharif","last_name":"Iqbal"},{"full_name":"Flanagan, Dustin J.","first_name":"Dustin J.","last_name":"Flanagan"},{"first_name":"David J.","full_name":"Huels, David J.","last_name":"Huels"},{"full_name":"Rojas-Rodríguez, Felipe","first_name":"Felipe","last_name":"Rojas-Rodríguez"},{"full_name":"Vizoso, Miguel","first_name":"Miguel","last_name":"Vizoso"},{"full_name":"Kasper, Maria","first_name":"Maria","last_name":"Kasper"},{"last_name":"Sansom","first_name":"Owen J.","full_name":"Sansom, Owen J."},{"last_name":"Snippert","first_name":"Hugo J.","full_name":"Snippert, Hugo J."},{"first_name":"Prisca","full_name":"Liberali, Prisca","last_name":"Liberali"},{"last_name":"Simons","first_name":"Benjamin D.","full_name":"Simons, Benjamin D."},{"full_name":"Katajisto, Pekka","first_name":"Pekka","last_name":"Katajisto"},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo"},{"last_name":"van Rheenen","first_name":"Jacco","full_name":"van Rheenen, Jacco"}],"isi":1,"page":"548-554","ec_funded":1,"volume":607,"quality_controlled":"1","article_type":"original","pmid":1,"publication":"Nature","publication_status":"published","fulldoi":"https://doi.org/10.1038/s41586-022-04962-0","oa":1,"date_published":"2022-07-13T00:00:00Z","date_created":"2023-01-16T10:01:29Z","issue":"7919","type":"journal_article","intvolume":"       607","related_material":{"link":[{"relation":"software","url":"https://github.com/JaccovanRheenenLab/Retrograde_movement_Azkanaz_Nature_2022"}]},"year":"2022","status":"public"},{"date_updated":"2025-04-14T07:52:26Z","ddc":["530"],"_id":"10365","publisher":"Springer Nature","external_id":{"isi":["000720204300004"]},"acknowledgement":"S.G. acknowledges funding from FEDER Prostem Research Project no. 1510614 (Wallonia DG06), F.R.S.-FNRS Epiforce Research Project no. T.0092.21 and Interreg MAT(T)ISSE project, which is financially supported by Interreg France-Wallonie-Vlaanderen (Fonds Européen de Développement Régional, FEDER-ERDF). This project was supported by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme grant agreement 851288 (to E.H.), and by the Austrian Science Fund (FWF) (P 31639; to E.H.). L.R.M. acknowledges funding from the Agence National de la Recherche (ANR), as part of the ‘Investments d’Avenir’ Programme (I-SITE ULNE/ANR-16-IDEX-0004 ULNE). This work benefited from ANR-10-EQPX-04-01 and FEDER 12001407 grants to F.L. W.D.V. is supported by the Research Foundation Flanders (FWO 1516619N, FWO GOO5819N, FWO I003420N, FWO IRI I000321N) and is member of the Research Excellence Consortium µNEURO at the University of Antwerp. M.L. is financially supported by FRIA (F.R.S.-FNRS). M.S. is a Senior Research Associate of the Fund for Scientific Research (F.R.S.-FNRS) and acknowledges EOS grant no. 30650939 (PRECISION). Sketches in Figs. 1a and 5e and Extended Data Fig. 9 were drawn by C. Levicek.","title":"Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation","article_processing_charge":"No","abstract":[{"text":"The early development of many organisms involves the folding of cell monolayers, but this behaviour is difficult to reproduce in vitro; therefore, both mechanistic causes and effects of local curvature remain unclear. Here we study epithelial cell monolayers on corrugated hydrogels engineered into wavy patterns, examining how concave and convex curvatures affect cellular and nuclear shape. We find that substrate curvature affects monolayer thickness, which is larger in valleys than crests. We show that this feature generically arises in a vertex model, leading to the hypothesis that cells may sense curvature by modifying the thickness of the tissue. We find that local curvature also affects nuclear morphology and positioning, which we explain by extending the vertex model to take into account membrane–nucleus interactions, encoding thickness modulation in changes to nuclear deformation and position. We propose that curvature governs the spatial distribution of yes-associated proteins via nuclear shape and density changes. We show that curvature also induces significant variations in lamins, chromatin condensation and cell proliferation rate in folded epithelial tissues. Together, this work identifies active cell mechanics and nuclear mechanoadaptation as the key players of the mechanistic regulation of epithelia to substrate curvature.","lang":"eng"}],"publication_identifier":{"eissn":["1745-2481"],"issn":["1745-2473"]},"citation":{"mla":"Luciano, Marine, et al. “Cell Monolayers Sense Curvature by Exploiting Active Mechanics and Nuclear Mechanoadaptation.” <i>Nature Physics</i>, vol. 17, no. 12, Springer Nature, 2021, pp. 1382–1390, doi:<a href=\"https://doi.org/10.1038/s41567-021-01374-1\">10.1038/s41567-021-01374-1</a>.","apa":"Luciano, M., Xue, S., De Vos, W. H., Redondo-Morata, L., Surin, M., Lafont, F., … Gabriele, S. (2021). Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-021-01374-1\">https://doi.org/10.1038/s41567-021-01374-1</a>","chicago":"Luciano, Marine, Shi-lei Xue, Winnok H. De Vos, Lorena Redondo-Morata, Mathieu Surin, Frank Lafont, Edouard B Hannezo, and Sylvain Gabriele. “Cell Monolayers Sense Curvature by Exploiting Active Mechanics and Nuclear Mechanoadaptation.” <i>Nature Physics</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41567-021-01374-1\">https://doi.org/10.1038/s41567-021-01374-1</a>.","short":"M. Luciano, S. Xue, W.H. De Vos, L. Redondo-Morata, M. Surin, F. Lafont, E.B. Hannezo, S. Gabriele, Nature Physics 17 (2021) 1382–1390.","ama":"Luciano M, Xue S, De Vos WH, et al. Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation. <i>Nature Physics</i>. 2021;17(12):1382–1390. doi:<a href=\"https://doi.org/10.1038/s41567-021-01374-1\">10.1038/s41567-021-01374-1</a>","ieee":"M. Luciano <i>et al.</i>, “Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation,” <i>Nature Physics</i>, vol. 17, no. 12. Springer Nature, pp. 1382–1390, 2021.","ista":"Luciano M, Xue S, De Vos WH, Redondo-Morata L, Surin M, Lafont F, Hannezo EB, Gabriele S. 2021. Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation. 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