[{"publication":"Cell","issue":"5","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"doi":"10.1016/j.cell.2022.01.022","year":"2022","date_created":"2022-03-06T23:01:52Z","ddc":["570"],"has_accepted_license":"1","quality_controlled":"1","file":[{"file_id":"10831","checksum":"ae305060e8031297771b89dae9e36a29","relation":"main_file","access_level":"open_access","date_updated":"2022-03-07T07:55:23Z","file_size":8478995,"date_created":"2022-03-07T07:55:23Z","file_name":"2022_Cell_Yanagida.pdf","content_type":"application/pdf","creator":"dernst","success":1}],"pmid":1,"volume":185,"author":[{"first_name":"Ayaka","last_name":"Yanagida","full_name":"Yanagida, Ayaka"},{"last_name":"Corujo-Simon","first_name":"Elena","full_name":"Corujo-Simon, Elena"},{"full_name":"Revell, Christopher K.","last_name":"Revell","first_name":"Christopher K."},{"first_name":"Preeti","last_name":"Sahu","full_name":"Sahu, Preeti","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E"},{"last_name":"Stirparo","first_name":"Giuliano G.","full_name":"Stirparo, Giuliano G."},{"full_name":"Aspalter, Irene M.","last_name":"Aspalter","first_name":"Irene M."},{"last_name":"Winkel","first_name":"Alex K.","full_name":"Winkel, Alex K."},{"full_name":"Peters, Ruby","first_name":"Ruby","last_name":"Peters"},{"first_name":"Henry","last_name":"De Belly","full_name":"De Belly, Henry"},{"full_name":"Cassani, Davide A.D.","last_name":"Cassani","first_name":"Davide A.D."},{"full_name":"Achouri, Sarra","last_name":"Achouri","first_name":"Sarra"},{"first_name":"Raphael","last_name":"Blumenfeld","full_name":"Blumenfeld, Raphael"},{"full_name":"Franze, Kristian","last_name":"Franze","first_name":"Kristian"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","last_name":"Hannezo","first_name":"Edouard B"},{"last_name":"Paluch","first_name":"Ewa K.","full_name":"Paluch, Ewa K."},{"full_name":"Nichols, Jennifer","last_name":"Nichols","first_name":"Jennifer"},{"last_name":"Chalut","first_name":"Kevin J.","full_name":"Chalut, Kevin J."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Cell surface fluctuations regulate early embryonic lineage sorting","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"}],"external_id":{"pmid":["35196500"],"isi":["000796293700007"]},"publication_status":"published","page":"777-793.e20","article_processing_charge":"No","status":"public","day":"22","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"project":[{"call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288"}],"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>.","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>.","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>","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>","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.","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.","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."},"_id":"10825","scopus_import":"1","type":"journal_article","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.","article_type":"original","intvolume":"       185","oa_version":"Published Version","department":[{"_id":"EdHa"}],"publisher":"Cell Press","date_updated":"2025-07-10T11:50:00Z","month":"02","language":[{"iso":"eng"}],"date_published":"2022-02-22T00:00:00Z","oa":1,"file_date_updated":"2022-03-07T07:55:23Z","isi":1},{"file_date_updated":"2023-01-27T07:32:01Z","oa":1,"isi":1,"date_updated":"2025-04-14T07:46:59Z","department":[{"_id":"CaHe"},{"_id":"EdHa"}],"publisher":"Springer Nature","date_published":"2022-12-01T00:00:00Z","language":[{"iso":"eng"}],"month":"12","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.).","type":"journal_article","intvolume":"        18","oa_version":"Published Version","article_type":"original","scopus_import":"1","_id":"12209","project":[{"grant_number":"ALTF 850-2017","_id":"26520D1E-B435-11E9-9278-68D0E5697425","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation"},{"grant_number":"ALTF 850-2017","_id":"26520D1E-B435-11E9-9278-68D0E5697425","name":"Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation"},{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis"},{"grant_number":"742573","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","call_identifier":"H2020"}],"citation":{"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>.","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>.","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.","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.","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>"},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"day":"01","status":"public","external_id":{"isi":["000871319900002"]},"publication_status":"published","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"}],"article_processing_charge":"No","page":"1482-1493","keyword":["General Physics and Astronomy"],"title":"Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming","volume":18,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Nunes Pinheiro, Diana C","id":"2E839F16-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4333-7503","last_name":"Nunes Pinheiro","first_name":"Diana C"},{"last_name":"Kardos","first_name":"Roland","id":"4039350E-F248-11E8-B48F-1D18A9856A87","full_name":"Kardos, Roland"},{"last_name":"Hannezo","first_name":"Edouard B","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"quality_controlled":"1","file":[{"file_id":"12412","file_size":36703569,"date_updated":"2023-01-27T07:32:01Z","checksum":"c86a8e8d80d1bfc46d56a01e88a2526a","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2022_NaturePhysics_Pinheiro.pdf","date_created":"2023-01-27T07:32:01Z","creator":"dernst","success":1}],"corr_author":"1","ddc":["570"],"has_accepted_license":"1","date_created":"2023-01-16T09:45:19Z","year":"2022","publication":"Nature Physics","doi":"10.1038/s41567-022-01787-6","publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"issue":"12"},{"citation":{"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>.","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>","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>.","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.","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>","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."},"project":[{"name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020","grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E"}],"status":"public","day":"05","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"month":"09","language":[{"iso":"eng"}],"date_published":"2022-09-05T00:00:00Z","publisher":"Springer Nature","department":[{"_id":"EdHa"}],"date_updated":"2025-06-11T13:53:55Z","isi":1,"oa":1,"file_date_updated":"2023-01-27T08:14:48Z","_id":"12217","scopus_import":"1","article_type":"original","oa_version":"Published Version","intvolume":"        13","type":"journal_article","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.","has_accepted_license":"1","ddc":["570"],"file":[{"creator":"dernst","success":1,"date_created":"2023-01-27T08:14:48Z","content_type":"application/pdf","file_name":"2022_NatureCommunications_Randriamanantsoa.pdf","checksum":"295261b5172274fd5b8f85a6a6058828","relation":"main_file","access_level":"open_access","date_updated":"2023-01-27T08:14:48Z","file_size":22645149,"file_id":"12416"}],"quality_controlled":"1","publication_identifier":{"issn":["2041-1723"]},"doi":"10.1038/s41467-022-32806-y","publication":"Nature Communications","year":"2022","date_created":"2023-01-16T09:46:53Z","article_number":"5219","title":"Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"article_processing_charge":"No","abstract":[{"lang":"eng","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."}],"publication_status":"published","external_id":{"isi":["000850348400025"],"pmid":["36064947"]},"related_material":{"record":[{"status":"public","relation":"research_data","id":"13068"}]},"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Randriamanantsoa","first_name":"S.","full_name":"Randriamanantsoa, S."},{"full_name":"Papargyriou, A.","first_name":"A.","last_name":"Papargyriou"},{"first_name":"H. C.","last_name":"Maurer","full_name":"Maurer, H. C."},{"last_name":"Peschke","first_name":"K.","full_name":"Peschke, K."},{"full_name":"Schuster, M.","last_name":"Schuster","first_name":"M."},{"full_name":"Zecchin, G.","first_name":"G.","last_name":"Zecchin"},{"full_name":"Steiger, K.","last_name":"Steiger","first_name":"K."},{"full_name":"Öllinger, R.","last_name":"Öllinger","first_name":"R."},{"full_name":"Saur, D.","first_name":"D.","last_name":"Saur"},{"full_name":"Scheel, C.","last_name":"Scheel","first_name":"C."},{"full_name":"Rad, R.","first_name":"R.","last_name":"Rad"},{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"last_name":"Reichert","first_name":"M.","full_name":"Reichert, M."},{"full_name":"Bausch, A. R.","last_name":"Bausch","first_name":"A. R."}],"volume":13},{"status":"public","day":"14","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"project":[{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020"}],"citation":{"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.","short":"J. Stock, T. Kazmar, F. Schlumm, E.B. Hannezo, A. Pauli, Science Advances 8 (2022).","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.","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>","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>","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>.","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>."},"_id":"12253","scopus_import":"1","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.","type":"journal_article","article_type":"original","oa_version":"Published Version","intvolume":"         8","publisher":"American Association for the Advancement of Science","department":[{"_id":"EdHa"}],"date_updated":"2025-04-14T07:52:27Z","month":"09","language":[{"iso":"eng"}],"date_published":"2022-09-14T00:00:00Z","oa":1,"file_date_updated":"2023-01-30T09:27:49Z","isi":1,"publication":"Science Advances","issue":"37","publication_identifier":{"issn":["2375-2548"]},"doi":"10.1126/sciadv.add2488","article_number":"eadd2488","year":"2022","date_created":"2023-01-16T09:57:10Z","ddc":["570"],"has_accepted_license":"1","quality_controlled":"1","file":[{"file_id":"12444","relation":"main_file","checksum":"f59cdb824e5d4221045def81f46f6c65","access_level":"open_access","file_size":1636732,"date_updated":"2023-01-30T09:27:49Z","date_created":"2023-01-30T09:27:49Z","content_type":"application/pdf","file_name":"2022_ScienceAdvances_Stock.pdf","creator":"dernst","success":1}],"pmid":1,"volume":8,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Jessica","last_name":"Stock","full_name":"Stock, Jessica"},{"full_name":"Kazmar, Tomas","first_name":"Tomas","last_name":"Kazmar"},{"last_name":"Schlumm","first_name":"Friederike","full_name":"Schlumm, Friederike"},{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"first_name":"Andrea","last_name":"Pauli","full_name":"Pauli, Andrea"}],"title":"A self-generated Toddler gradient guides mesodermal cell migration","abstract":[{"lang":"eng","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."}],"publication_status":"published","external_id":{"pmid":["36103529"],"isi":["000888875000009"]},"article_processing_charge":"No"},{"main_file_link":[{"url":"https://helda.helsinki.fi/items/94433455-4854-45c0-9de8-7326caea8780","open_access":"1"}],"corr_author":"1","quality_controlled":"1","issue":"7919","doi":"10.1038/s41586-022-04962-0","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"publication":"Nature","year":"2022","date_created":"2023-01-16T10:01:29Z","title":"Retrograde movements determine effective stem cell numbers in the intestine","keyword":["Multidisciplinary"],"page":"548-554","article_processing_charge":"No","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."}],"external_id":{"pmid":["35831497"],"isi":["000824430000004"]},"publication_status":"published","related_material":{"link":[{"relation":"software","url":"https://github.com/JaccovanRheenenLab/Retrograde_movement_Azkanaz_Nature_2022"}]},"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Azkanaz","first_name":"Maria","full_name":"Azkanaz, Maria"},{"first_name":"Bernat","last_name":"Corominas-Murtra","orcid":"0000-0001-9806-5643","id":"43BE2298-F248-11E8-B48F-1D18A9856A87","full_name":"Corominas-Murtra, Bernat"},{"full_name":"Ellenbroek, Saskia I. J.","last_name":"Ellenbroek","first_name":"Saskia I. J."},{"first_name":"Lotte","last_name":"Bruens","full_name":"Bruens, Lotte"},{"first_name":"Anna T.","last_name":"Webb","full_name":"Webb, Anna T."},{"full_name":"Laskaris, Dimitrios","first_name":"Dimitrios","last_name":"Laskaris"},{"last_name":"Oost","first_name":"Koen C.","full_name":"Oost, Koen C."},{"first_name":"Simona J. A.","last_name":"Lafirenze","full_name":"Lafirenze, Simona J. A."},{"full_name":"Annusver, Karl","first_name":"Karl","last_name":"Annusver"},{"last_name":"Messal","first_name":"Hendrik A.","full_name":"Messal, Hendrik A."},{"last_name":"Iqbal","first_name":"Sharif","full_name":"Iqbal, Sharif"},{"full_name":"Flanagan, Dustin J.","last_name":"Flanagan","first_name":"Dustin J."},{"full_name":"Huels, David J.","last_name":"Huels","first_name":"David J."},{"full_name":"Rojas-Rodríguez, Felipe","first_name":"Felipe","last_name":"Rojas-Rodríguez"},{"first_name":"Miguel","last_name":"Vizoso","full_name":"Vizoso, Miguel"},{"last_name":"Kasper","first_name":"Maria","full_name":"Kasper, Maria"},{"first_name":"Owen J.","last_name":"Sansom","full_name":"Sansom, Owen J."},{"last_name":"Snippert","first_name":"Hugo J.","full_name":"Snippert, Hugo J."},{"full_name":"Liberali, Prisca","last_name":"Liberali","first_name":"Prisca"},{"full_name":"Simons, Benjamin D.","last_name":"Simons","first_name":"Benjamin D."},{"first_name":"Pekka","last_name":"Katajisto","full_name":"Katajisto, Pekka"},{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jacco","last_name":"van Rheenen","full_name":"van Rheenen, Jacco"}],"volume":607,"citation":{"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.","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.","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>","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.","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>.","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>","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>."},"project":[{"call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis","_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288"}],"day":"13","status":"public","ec_funded":1,"month":"07","language":[{"iso":"eng"}],"date_published":"2022-07-13T00:00:00Z","publisher":"Springer Nature","department":[{"_id":"EdHa"}],"date_updated":"2025-04-14T07:52:27Z","isi":1,"oa":1,"_id":"12274","scopus_import":"1","article_type":"original","oa_version":"Submitted Version","intvolume":"       607","type":"journal_article","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)."},{"title":"Geometry adaptation of protrusion and polarity dynamics in confined cell migration","keyword":["General Physics and Astronomy"],"abstract":[{"text":"Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive self-reinforcing feedback loop. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.","lang":"eng"}],"publication_status":"published","external_id":{"arxiv":["2106.01014"],"isi":["000861534700001"]},"article_processing_charge":"No","volume":12,"author":[{"full_name":"Brückner, David","id":"e1e86031-6537-11eb-953a-f7ab92be508d","orcid":"0000-0001-7205-2975","first_name":"David","last_name":"Brückner"},{"first_name":"Matthew","last_name":"Schmitt","full_name":"Schmitt, Matthew"},{"last_name":"Fink","first_name":"Alexandra","full_name":"Fink, Alexandra"},{"full_name":"Ladurner, Georg","last_name":"Ladurner","first_name":"Georg"},{"full_name":"Flommersfeld, Johannes","first_name":"Johannes","last_name":"Flommersfeld"},{"full_name":"Arlt, Nicolas","last_name":"Arlt","first_name":"Nicolas"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","last_name":"Hannezo","first_name":"Edouard B"},{"last_name":"Rädler","first_name":"Joachim O.","full_name":"Rädler, Joachim O."},{"first_name":"Chase P.","last_name":"Broedersz","full_name":"Broedersz, Chase P."}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["530","570"],"has_accepted_license":"1","file":[{"file_id":"12458","date_updated":"2023-01-30T11:07:27Z","file_size":4686804,"access_level":"open_access","relation":"main_file","checksum":"40a8fbc3663bf07b37cb80020974d40d","file_name":"2022_PhysicalReviewX_Brueckner.pdf","content_type":"application/pdf","date_created":"2023-01-30T11:07:27Z","success":1,"creator":"dernst"}],"quality_controlled":"1","publication":"Physical Review X","issue":"3","publication_identifier":{"issn":["2160-3308"]},"doi":"10.1103/physrevx.12.031041","article_number":"031041","year":"2022","date_created":"2023-01-16T10:02:06Z","arxiv":1,"publisher":"American Physical Society","department":[{"_id":"EdHa"}],"date_updated":"2023-08-04T10:25:49Z","language":[{"iso":"eng"}],"month":"09","date_published":"2022-09-20T00:00:00Z","oa":1,"file_date_updated":"2023-01-30T11:07:27Z","isi":1,"_id":"12277","scopus_import":"1","type":"journal_article","acknowledgement":"We thank Grzegorz Gradziuk, StevenRiedijk, Janni Harju, and M. R. Schnucki for helpful discussions, and Andriy Goychuk for advice on the image segmentation. This project\r\nwas funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project No. 201269156—SFB 1032 (Projects B01 and B12). D. B. B. is supported by the NOMIS Foundation and in part by a DFG fellowship within the Graduate School of Quantitative Biosciences Munich (QBM), as well as by the Joachim Herz Stiftung.","article_type":"original","intvolume":"        12","oa_version":"Published Version","citation":{"short":"D. Brückner, M. Schmitt, A. Fink, G. Ladurner, J. Flommersfeld, N. Arlt, E.B. Hannezo, J.O. Rädler, C.P. Broedersz, Physical Review X 12 (2022).","ieee":"D. Brückner <i>et al.</i>, “Geometry adaptation of protrusion and polarity dynamics in confined cell migration,” <i>Physical Review X</i>, vol. 12, no. 3. American Physical Society, 2022.","ista":"Brückner D, Schmitt M, Fink A, Ladurner G, Flommersfeld J, Arlt N, Hannezo EB, Rädler JO, Broedersz CP. 2022. Geometry adaptation of protrusion and polarity dynamics in confined cell migration. Physical Review X. 12(3), 031041.","ama":"Brückner D, Schmitt M, Fink A, et al. Geometry adaptation of protrusion and polarity dynamics in confined cell migration. <i>Physical Review X</i>. 2022;12(3). doi:<a href=\"https://doi.org/10.1103/physrevx.12.031041\">10.1103/physrevx.12.031041</a>","apa":"Brückner, D., Schmitt, M., Fink, A., Ladurner, G., Flommersfeld, J., Arlt, N., … Broedersz, C. P. (2022). Geometry adaptation of protrusion and polarity dynamics in confined cell migration. <i>Physical Review X</i>. American Physical Society. <a href=\"https://doi.org/10.1103/physrevx.12.031041\">https://doi.org/10.1103/physrevx.12.031041</a>","chicago":"Brückner, David, Matthew Schmitt, Alexandra Fink, Georg Ladurner, Johannes Flommersfeld, Nicolas Arlt, Edouard B Hannezo, Joachim O. Rädler, and Chase P. Broedersz. “Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration.” <i>Physical Review X</i>. American Physical Society, 2022. <a href=\"https://doi.org/10.1103/physrevx.12.031041\">https://doi.org/10.1103/physrevx.12.031041</a>.","mla":"Brückner, David, et al. “Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration.” <i>Physical Review X</i>, vol. 12, no. 3, 031041, American Physical Society, 2022, doi:<a href=\"https://doi.org/10.1103/physrevx.12.031041\">10.1103/physrevx.12.031041</a>."},"day":"20","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"}},{"citation":{"mla":"Zisis, Themistoklis, et al. “Disentangling Cadherin-Mediated Cell-Cell Interactions in Collective Cancer Cell Migration.” <i>Biophysical Journal</i>, vol. 121, no. 1, Elsevier, 2022, pp. P44-60, doi:<a href=\"https://doi.org/10.1016/j.bpj.2021.12.006\">10.1016/j.bpj.2021.12.006</a>.","chicago":"Zisis, Themistoklis, David Brückner, Tom Brandstätter, Wei Xiong Siow, Joseph d’Alessandro, Angelika M. Vollmar, Chase P. Broedersz, and Stefan Zahler. “Disentangling Cadherin-Mediated Cell-Cell Interactions in Collective Cancer Cell Migration.” <i>Biophysical Journal</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.bpj.2021.12.006\">https://doi.org/10.1016/j.bpj.2021.12.006</a>.","apa":"Zisis, T., Brückner, D., Brandstätter, T., Siow, W. X., d’Alessandro, J., Vollmar, A. M., … Zahler, S. (2022). Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration. <i>Biophysical Journal</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.bpj.2021.12.006\">https://doi.org/10.1016/j.bpj.2021.12.006</a>","ama":"Zisis T, Brückner D, Brandstätter T, et al. Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration. <i>Biophysical Journal</i>. 2022;121(1):P44-60. doi:<a href=\"https://doi.org/10.1016/j.bpj.2021.12.006\">10.1016/j.bpj.2021.12.006</a>","ista":"Zisis T, Brückner D, Brandstätter T, Siow WX, d’Alessandro J, Vollmar AM, Broedersz CP, Zahler S. 2022. Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration. Biophysical Journal. 121(1), P44-60.","ieee":"T. Zisis <i>et al.</i>, “Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration,” <i>Biophysical Journal</i>, vol. 121, no. 1. Elsevier, pp. P44-60, 2022.","short":"T. Zisis, D. Brückner, T. Brandstätter, W.X. Siow, J. d’Alessandro, A.M. Vollmar, C.P. Broedersz, S. Zahler, Biophysical Journal 121 (2022) P44-60."},"project":[{"name":"NOMIS Fellowship Program","_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A"}],"tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"day":"04","status":"public","isi":1,"oa":1,"file_date_updated":"2022-07-29T10:17:10Z","month":"01","language":[{"iso":"eng"}],"date_published":"2022-01-04T00:00:00Z","department":[{"_id":"EdHa"},{"_id":"GaTk"}],"publisher":"Elsevier","date_updated":"2025-06-11T13:59:29Z","article_type":"original","intvolume":"       121","oa_version":"Published Version","type":"journal_article","acknowledgement":"Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Project-ID 201269156 - SFB 1032 (Projects B8 and B12). D.B.B. is supported in part by a DFG fellowship within the Graduate School of Quantitative Biosciences Munich (QBM) and by the Joachim Herz Stiftung.","_id":"10530","scopus_import":"1","quality_controlled":"1","file":[{"file_id":"11697","relation":"main_file","checksum":"1aa7c3478e0c8256b973b632efd1f6b4","access_level":"open_access","date_updated":"2022-07-29T10:17:10Z","file_size":4475504,"date_created":"2022-07-29T10:17:10Z","file_name":"2022_BiophysicalJour_Zisis.pdf","content_type":"application/pdf","creator":"dernst","success":1}],"has_accepted_license":"1","ddc":["570"],"year":"2022","date_created":"2021-12-10T09:48:19Z","issue":"1","publication_identifier":{"issn":["0006-3495"]},"doi":"10.1016/j.bpj.2021.12.006","publication":"Biophysical Journal","page":"P44-60","article_processing_charge":"No","abstract":[{"lang":"eng","text":"Cell dispersion from a confined area is fundamental in a number of biological processes,\r\nincluding cancer metastasis. To date, a quantitative understanding of the interplay of single\r\ncell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role\r\nof E- and N-Cadherin junctions, central components of intercellular contacts, is still\r\ncontroversial. Combining theoretical modeling with in vitro observations, we investigate the\r\ncollective spreading behavior of colonies of human cancer cells (T24). The spreading of these\r\ncolonies is driven by stochastic single-cell migration with frequent transient cell-cell contacts.\r\nWe find that inhibition of E- and N-Cadherin junctions decreases colony spreading and average\r\nspreading velocities, without affecting the strength of correlations in spreading velocities of\r\nneighboring cells. Based on a biophysical simulation model for cell migration, we show that the\r\nbehavioral changes upon disruption of these junctions can be explained by reduced repulsive\r\nexcluded volume interactions between cells. This suggests that in cancer cell migration,\r\ncadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than\r\ncohesive interactions between cells, thereby promoting efficient cell spreading during collective\r\nmigration.\r\n"}],"publication_status":"published","external_id":{"isi":["000740815400007"],"pmid":["34890578"]},"title":"Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration","keyword":["Biophysics"],"author":[{"full_name":"Zisis, Themistoklis","first_name":"Themistoklis","last_name":"Zisis"},{"last_name":"Brückner","first_name":"David","full_name":"Brückner, David","id":"e1e86031-6537-11eb-953a-f7ab92be508d","orcid":"0000-0001-7205-2975"},{"last_name":"Brandstätter","first_name":"Tom","full_name":"Brandstätter, Tom"},{"last_name":"Siow","first_name":"Wei Xiong","full_name":"Siow, Wei Xiong"},{"full_name":"d’Alessandro, Joseph","last_name":"d’Alessandro","first_name":"Joseph"},{"full_name":"Vollmar, Angelika M.","last_name":"Vollmar","first_name":"Angelika M."},{"last_name":"Broedersz","first_name":"Chase P.","full_name":"Broedersz, Chase P."},{"last_name":"Zahler","first_name":"Stefan","full_name":"Zahler, Stefan"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":121,"pmid":1},{"page":"P433-444","article_processing_charge":"No","abstract":[{"text":"Although rigidity and jamming transitions have been widely studied in physics and material science, their importance in a number of biological processes, including embryo development, tissue homeostasis, wound healing, and disease progression, has only begun to be recognized in the past few years. The hypothesis that biological systems can undergo rigidity/jamming transitions is attractive, as it would allow these systems to change their material properties rapidly and strongly. However, whether such transitions indeed occur in biological systems, how they are being regulated, and what their physiological relevance might be, is still being debated. Here, we review theoretical and experimental advances from the past few years, focusing on the regulation and role of potential tissue rigidity transitions in different biological processes.","lang":"eng"}],"publication_status":"published","external_id":{"pmid":["35058104"],"isi":["000795773900009"]},"title":"Rigidity transitions in development and disease","author":[{"full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","last_name":"Hannezo","first_name":"Edouard B"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","volume":32,"pmid":1,"corr_author":"1","quality_controlled":"1","year":"2022","date_created":"2022-01-30T23:01:34Z","issue":"5","publication_identifier":{"issn":["0962-8924"],"eissn":["1879-3088"]},"doi":"10.1016/j.tcb.2021.12.006","publication":"Trends in Cell Biology","isi":1,"month":"05","language":[{"iso":"eng"}],"date_published":"2022-05-01T00:00:00Z","department":[{"_id":"EdHa"},{"_id":"CaHe"}],"publisher":"Cell Press","date_updated":"2024-10-09T21:01:30Z","article_type":"original","oa_version":"None","intvolume":"        32","acknowledgement":"We thank present and former members of the Heisenberg and Hannezo groups, in particular Bernat Corominas-Murtra and Nicoletta Petridou, for helpful discussions, and Claudia Flandoli for the artwork. We apologize for not being able to cite a number of highly relevant studies, to stay within the maximum allowed number of citations.","type":"journal_article","_id":"10705","scopus_import":"1","citation":{"ama":"Hannezo EB, Heisenberg C-PJ. Rigidity transitions in development and disease. <i>Trends in Cell Biology</i>. 2022;32(5):P433-444. doi:<a href=\"https://doi.org/10.1016/j.tcb.2021.12.006\">10.1016/j.tcb.2021.12.006</a>","ista":"Hannezo EB, Heisenberg C-PJ. 2022. Rigidity transitions in development and disease. Trends in Cell Biology. 32(5), P433-444.","short":"E.B. Hannezo, C.-P.J. Heisenberg, Trends in Cell Biology 32 (2022) P433-444.","ieee":"E. B. Hannezo and C.-P. J. Heisenberg, “Rigidity transitions in development and disease,” <i>Trends in Cell Biology</i>, vol. 32, no. 5. Cell Press, pp. P433-444, 2022.","mla":"Hannezo, Edouard B., and Carl-Philipp J. Heisenberg. “Rigidity Transitions in Development and Disease.” <i>Trends in Cell Biology</i>, vol. 32, no. 5, Cell Press, 2022, pp. P433-444, doi:<a href=\"https://doi.org/10.1016/j.tcb.2021.12.006\">10.1016/j.tcb.2021.12.006</a>.","apa":"Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2022). Rigidity transitions in development and disease. <i>Trends in Cell Biology</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.tcb.2021.12.006\">https://doi.org/10.1016/j.tcb.2021.12.006</a>","chicago":"Hannezo, Edouard B, and Carl-Philipp J Heisenberg. “Rigidity Transitions in Development and Disease.” <i>Trends in Cell Biology</i>. Cell Press, 2022. <a href=\"https://doi.org/10.1016/j.tcb.2021.12.006\">https://doi.org/10.1016/j.tcb.2021.12.006</a>."},"status":"public","day":"01"},{"corr_author":"1","file":[{"success":1,"creator":"dernst","date_created":"2022-07-25T07:11:32Z","file_name":"2022_NatureImmunology_Assen.pdf","content_type":"application/pdf","access_level":"open_access","checksum":"628e7b49809f22c75b428842efe70c68","relation":"main_file","file_size":11475325,"date_updated":"2022-07-25T07:11:32Z","file_id":"11642"}],"quality_controlled":"1","has_accepted_license":"1","ddc":["570"],"year":"2022","date_created":"2021-08-06T09:09:11Z","publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]},"doi":"10.1038/s41590-022-01257-4","publication":"Nature Immunology","page":"1246-1255","article_processing_charge":"No","abstract":[{"lang":"eng","text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion."}],"publication_status":"published","external_id":{"isi":["000822975900002"],"pmid":["35817845"]},"title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","author":[{"full_name":"Assen, Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119","first_name":"Frank P","last_name":"Assen"},{"last_name":"Abe","first_name":"Jun","full_name":"Abe, Jun"},{"first_name":"Miroslav","last_name":"Hons","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav"},{"full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","last_name":"Hauschild"},{"last_name":"Shamipour","first_name":"Shayan","full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter","first_name":"Walter","last_name":"Kaufmann"},{"id":"D93824F4-D9BA-11E9-BB12-F207E6697425","orcid":"0000-0001-9732-3815","full_name":"Costanzo, Tommaso","first_name":"Tommaso","last_name":"Costanzo"},{"full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","last_name":"Krens"},{"full_name":"Brown, Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","last_name":"Brown","first_name":"Markus"},{"last_name":"Ludewig","first_name":"Burkhard","full_name":"Ludewig, Burkhard"},{"first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"},{"full_name":"Weninger, Wolfgang","first_name":"Wolfgang","last_name":"Weninger"},{"last_name":"Hannezo","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B"},{"last_name":"Luther","first_name":"Sanjiv A.","full_name":"Luther, Sanjiv A."},{"last_name":"Stein","first_name":"Jens V.","full_name":"Stein, Jens V."},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X","last_name":"Sixt","first_name":"Michael K"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":23,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"pmid":1,"citation":{"ieee":"F. P. Assen <i>et al.</i>, “Multitier mechanics control stromal adaptations in swelling lymph nodes,” <i>Nature Immunology</i>, vol. 23. Springer Nature, pp. 1246–1255, 2022.","short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. 2022;23:1246-1255. doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>","ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255.","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>.","apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>."},"project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients"}],"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"11","status":"public","isi":1,"oa":1,"file_date_updated":"2022-07-25T07:11:32Z","language":[{"iso":"eng"}],"month":"07","date_published":"2022-07-11T00:00:00Z","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"publisher":"Springer Nature","date_updated":"2025-06-11T13:52:43Z","article_type":"original","intvolume":"        23","oa_version":"Published Version","type":"journal_article","acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","_id":"9794","scopus_import":"1"},{"date_created":"2023-05-23T13:46:34Z","year":"2021","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"doi":"10.5281/ZENODO.5257160","status":"public","day":"25","citation":{"ieee":"M. C. Ucar, “Source data for the manuscript ‘Theory of branching morphogenesis by local interactions and global guidance.’” Zenodo, 2021.","short":"M.C. Ucar, (2021).","ista":"Ucar MC. 2021. Source data for the manuscript ‘Theory of branching morphogenesis by local interactions and global guidance’, Zenodo, <a href=\"https://doi.org/10.5281/ZENODO.5257160\">10.5281/ZENODO.5257160</a>.","ama":"Ucar MC. Source data for the manuscript “Theory of branching morphogenesis by local interactions and global guidance.” 2021. doi:<a href=\"https://doi.org/10.5281/ZENODO.5257160\">10.5281/ZENODO.5257160</a>","chicago":"Ucar, Mehmet C. “Source Data for the Manuscript ‘Theory of Branching Morphogenesis by Local Interactions and Global Guidance.’” Zenodo, 2021. <a href=\"https://doi.org/10.5281/ZENODO.5257160\">https://doi.org/10.5281/ZENODO.5257160</a>.","apa":"Ucar, M. C. (2021). Source data for the manuscript “Theory of branching morphogenesis by local interactions and global guidance.” Zenodo. <a href=\"https://doi.org/10.5281/ZENODO.5257160\">https://doi.org/10.5281/ZENODO.5257160</a>","mla":"Ucar, Mehmet C. <i>Source Data for the Manuscript “Theory of Branching Morphogenesis by Local Interactions and Global Guidance.”</i> Zenodo, 2021, doi:<a href=\"https://doi.org/10.5281/ZENODO.5257160\">10.5281/ZENODO.5257160</a>."},"corr_author":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.5281/zenodo.5257161"}],"ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Ucar, Mehmet C","orcid":"0000-0003-0506-4217","id":"50B2A802-6007-11E9-A42B-EB23E6697425","first_name":"Mehmet C","last_name":"Ucar"}],"oa_version":"Published Version","type":"research_data_reference","related_material":{"record":[{"relation":"used_in_publication","id":"10402","status":"public"}]},"_id":"13058","article_processing_charge":"No","oa":1,"abstract":[{"lang":"eng","text":"The zip file includes source data used in the main text of the manuscript \"Theory of branching morphogenesis by local interactions and global guidance\", as well as a representative Jupyter notebook to reproduce the main figures. A sample script for the simulations of branching and annihilating random walks is also included (Sample_script_for_simulations_of_BARWs.ipynb) to generate exemplary branched networks under external guidance. A detailed description of the simulation setup is provided in the supplementary information of the manuscipt."}],"date_published":"2021-08-25T00:00:00Z","month":"08","title":"Source data for the manuscript \"Theory of branching morphogenesis by local interactions and global guidance\"","date_updated":"2025-04-15T06:54:54Z","publisher":"Zenodo","department":[{"_id":"EdHa"}]},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"year":"2021","date_created":"2023-05-23T16:39:24Z","status":"public","day":"30","doi":"10.5281/ZENODO.5148117","citation":{"mla":"Randriamanantsoa, Samuel, et al. <i>Spatiotemporal Dynamics of Self-Organized Branching in Pancreas-Derived Organoids</i>. Zenodo, 2021, doi:<a href=\"https://doi.org/10.5281/ZENODO.5148117\">10.5281/ZENODO.5148117</a>.","apa":"Randriamanantsoa, S., Papargyriou, A., Maurer, C., Peschke, K., Schuster, M., Zecchin, G., … Bausch, A. R. (2021). Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. Zenodo. <a href=\"https://doi.org/10.5281/ZENODO.5148117\">https://doi.org/10.5281/ZENODO.5148117</a>","chicago":"Randriamanantsoa, Samuel, Aristeidis Papargyriou, Carlo Maurer, Katja Peschke, Maximilian Schuster, Giulia Zecchin, Katja Steiger, et al. “Spatiotemporal Dynamics of Self-Organized Branching in Pancreas-Derived Organoids.” Zenodo, 2021. <a href=\"https://doi.org/10.5281/ZENODO.5148117\">https://doi.org/10.5281/ZENODO.5148117</a>.","ama":"Randriamanantsoa S, Papargyriou A, Maurer C, et al. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. 2021. doi:<a href=\"https://doi.org/10.5281/ZENODO.5148117\">10.5281/ZENODO.5148117</a>","ista":"Randriamanantsoa S, Papargyriou A, Maurer C, Peschke K, Schuster M, Zecchin G, Steiger K, Öllinger R, Saur D, Scheel C, Rad R, Hannezo EB, Reichert M, Bausch AR. 2021. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids, Zenodo, <a href=\"https://doi.org/10.5281/ZENODO.5148117\">10.5281/ZENODO.5148117</a>.","short":"S. Randriamanantsoa, A. Papargyriou, 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, (2021).","ieee":"S. Randriamanantsoa <i>et al.</i>, “Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids.” Zenodo, 2021."},"ddc":["570"],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5281/zenodo.6577226"}],"type":"research_data_reference","oa_version":"Published Version","author":[{"full_name":"Randriamanantsoa, Samuel","first_name":"Samuel","last_name":"Randriamanantsoa"},{"full_name":"Papargyriou, Aristeidis","first_name":"Aristeidis","last_name":"Papargyriou"},{"full_name":"Maurer, Carlo","first_name":"Carlo","last_name":"Maurer"},{"full_name":"Peschke, Katja","last_name":"Peschke","first_name":"Katja"},{"first_name":"Maximilian","last_name":"Schuster","full_name":"Schuster, Maximilian"},{"full_name":"Zecchin, Giulia","last_name":"Zecchin","first_name":"Giulia"},{"full_name":"Steiger, Katja","first_name":"Katja","last_name":"Steiger"},{"first_name":"Rupert","last_name":"Öllinger","full_name":"Öllinger, Rupert"},{"last_name":"Saur","first_name":"Dieter","full_name":"Saur, Dieter"},{"first_name":"Christina","last_name":"Scheel","full_name":"Scheel, Christina"},{"last_name":"Rad","first_name":"Roland","full_name":"Rad, Roland"},{"last_name":"Hannezo","first_name":"Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B"},{"last_name":"Reichert","first_name":"Maximilian","full_name":"Reichert, Maximilian"},{"full_name":"Bausch, Andreas R.","first_name":"Andreas R.","last_name":"Bausch"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"status":"public","id":"12217","relation":"used_in_publication"}]},"_id":"13068","abstract":[{"lang":"eng","text":"Source data and source code for the graphs in \"Spatiotemporal dynamics of self-organized branching pancreatic cancer-derived organoids\"."}],"oa":1,"article_processing_charge":"No","department":[{"_id":"EdHa"}],"publisher":"Zenodo","date_updated":"2025-06-11T13:53:54Z","title":"Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids","month":"07","date_published":"2021-07-30T00:00:00Z"},{"external_id":{"isi":["000702042400001"],"arxiv":["2102.05397"]},"publication_status":"published","abstract":[{"text":"In dense biological tissues, cell types performing different roles remain segregated by maintaining sharp interfaces. To better understand the mechanisms for such sharp compartmentalization, we study the effect of an imposed heterotypic tension at the interface between two distinct cell types in a fully 3D Voronoi model for confluent tissues. We find that cells rapidly sort and self-organize to generate a tissue-scale interface between cell types, and cells adjacent to this interface exhibit signature geometric features including nematic-like ordering, bimodal facet areas, and registration, or alignment, of cell centers on either side of the two-tissue interface. The magnitude of these features scales directly with the magnitude of the imposed tension, suggesting that biologists can estimate the magnitude of tissue surface tension between two tissue types simply by segmenting a 3D tissue. To uncover the underlying physical mechanisms driving these geometric features, we develop two minimal, ordered models using two different underlying lattices that identify an energetic competition between bulk cell shapes and tissue interface area. When the interface area dominates, changes to neighbor topology are costly and occur less frequently, which generates the observed geometric features.","lang":"eng"}],"article_processing_charge":"Yes","title":"Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue","volume":23,"author":[{"full_name":"Sahu, Preeti","id":"55BA52EE-A185-11EA-88FD-18AD3DDC885E","first_name":"Preeti","last_name":"Sahu"},{"last_name":"Schwarz","first_name":"J. M.","full_name":"Schwarz, J. M."},{"full_name":"Manning, M. Lisa","first_name":"M. Lisa","last_name":"Manning"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file":[{"success":1,"creator":"cziletti","content_type":"application/pdf","file_name":"2021_NewJPhys_Sahu.pdf","date_created":"2021-10-28T12:06:01Z","file_size":2215016,"date_updated":"2021-10-28T12:06:01Z","access_level":"open_access","relation":"main_file","checksum":"ace603e8f0962b3ba55f23fa34f57764","file_id":"10193"}],"quality_controlled":"1","ddc":["570"],"has_accepted_license":"1","article_number":"093043","date_created":"2021-10-24T22:01:34Z","year":"2021","publication":"New Journal of Physics","doi":"10.1088/1367-2630/ac23f1","publication_identifier":{"eissn":["1367-2630"]},"issue":"9","file_date_updated":"2021-10-28T12:06:01Z","oa":1,"isi":1,"date_updated":"2026-04-02T13:54:56Z","publisher":"IOP Publishing","arxiv":1,"department":[{"_id":"EdHa"}],"date_published":"2021-09-29T00:00:00Z","month":"09","language":[{"iso":"eng"}],"acknowledgement":"We thank Paula Sanematsu, Matthias Merkel, Daniel Sussman, Cristina Marchetti and Edouard Hannezo for helpful discussions, and M Merkel for developing and sharing the original version of the 3D Voronoi code. This work was primarily funded by NSF-PHY-1607416, NSF-PHY-2014192 , and are in the division of physics at the National Science Foundation. PS and MLM acknowledge additional support from Simons Grant No. 454947.\r\n","type":"journal_article","intvolume":"        23","oa_version":"Published Version","article_type":"original","scopus_import":"1","_id":"10178","citation":{"chicago":"Sahu, Preeti, J. M. Schwarz, and M. Lisa Manning. “Geometric Signatures of Tissue Surface Tension in a Three-Dimensional Model of Confluent Tissue.” <i>New Journal of Physics</i>. IOP Publishing, 2021. <a href=\"https://doi.org/10.1088/1367-2630/ac23f1\">https://doi.org/10.1088/1367-2630/ac23f1</a>.","apa":"Sahu, P., Schwarz, J. M., &#38; Manning, M. L. (2021). Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue. <i>New Journal of Physics</i>. IOP Publishing. <a href=\"https://doi.org/10.1088/1367-2630/ac23f1\">https://doi.org/10.1088/1367-2630/ac23f1</a>","mla":"Sahu, Preeti, et al. “Geometric Signatures of Tissue Surface Tension in a Three-Dimensional Model of Confluent Tissue.” <i>New Journal of Physics</i>, vol. 23, no. 9, 093043, IOP Publishing, 2021, doi:<a href=\"https://doi.org/10.1088/1367-2630/ac23f1\">10.1088/1367-2630/ac23f1</a>.","ieee":"P. Sahu, J. M. Schwarz, and M. L. Manning, “Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue,” <i>New Journal of Physics</i>, vol. 23, no. 9. IOP Publishing, 2021.","short":"P. Sahu, J.M. Schwarz, M.L. Manning, New Journal of Physics 23 (2021).","ama":"Sahu P, Schwarz JM, Manning ML. Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue. <i>New Journal of Physics</i>. 2021;23(9). doi:<a href=\"https://doi.org/10.1088/1367-2630/ac23f1\">10.1088/1367-2630/ac23f1</a>","ista":"Sahu P, Schwarz JM, Manning ML. 2021. Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue. New Journal of Physics. 23(9), 093043."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"29","status":"public"},{"citation":{"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.","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.","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. Nature Physics. 17(12), 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>","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>.","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>."},"project":[{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis"},{"call_identifier":"FWF","name":"Active mechano-chemical description of the cell cytoskeleton","_id":"268294B6-B435-11E9-9278-68D0E5697425","grant_number":"P31639"}],"day":"18","status":"public","ec_funded":1,"language":[{"iso":"eng"}],"month":"11","date_published":"2021-11-18T00:00:00Z","department":[{"_id":"EdHa"}],"publisher":"Springer Nature","date_updated":"2025-04-14T07:52:26Z","isi":1,"oa":1,"file_date_updated":"2023-10-11T09:31:43Z","_id":"10365","scopus_import":"1","article_type":"original","oa_version":"Submitted Version","intvolume":"        17","type":"journal_article","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.","has_accepted_license":"1","ddc":["530"],"corr_author":"1","quality_controlled":"1","file":[{"date_created":"2023-10-11T09:31:43Z","content_type":"application/pdf","file_name":"50145_4_merged_1630498627.pdf","success":1,"creator":"channezo","file_id":"14420","access_level":"open_access","checksum":"5d6d76750a71d7cb632bb15417c38ef7","relation":"main_file","date_updated":"2023-10-11T09:31:43Z","file_size":40285498}],"issue":"12","publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"doi":"10.1038/s41567-021-01374-1","publication":"Nature Physics","year":"2021","date_created":"2021-11-28T23:01:29Z","title":"Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation","page":"1382–1390","article_processing_charge":"No","abstract":[{"lang":"eng","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."}],"publication_status":"published","external_id":{"isi":["000720204300004"]},"related_material":{"link":[{"url":"https://ist.ac.at/en/news/how-cells-feel-curvature/","relation":"press_release","description":"News on IST Webpage"}]},"author":[{"full_name":"Luciano, Marine","last_name":"Luciano","first_name":"Marine"},{"first_name":"Shi-lei","last_name":"Xue","id":"31D2C804-F248-11E8-B48F-1D18A9856A87","full_name":"Xue, Shi-lei"},{"full_name":"De Vos, Winnok H.","first_name":"Winnok H.","last_name":"De Vos"},{"first_name":"Lorena","last_name":"Redondo-Morata","full_name":"Redondo-Morata, Lorena"},{"last_name":"Surin","first_name":"Mathieu","full_name":"Surin, Mathieu"},{"last_name":"Lafont","first_name":"Frank","full_name":"Lafont, Frank"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","first_name":"Edouard B","last_name":"Hannezo"},{"full_name":"Gabriele, Sylvain","first_name":"Sylvain","last_name":"Gabriele"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":17},{"project":[{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020"},{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"citation":{"apa":"Ucar, M. C., Kamenev, D., Sunadome, K., Fachet, D. C., Lallemend, F., Adameyko, I., … Hannezo, E. B. (2021). Theory of branching morphogenesis by local interactions and global guidance. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-27135-5\">https://doi.org/10.1038/s41467-021-27135-5</a>","chicago":"Ucar, Mehmet C, Dmitrii Kamenev, Kazunori Sunadome, Dominik C Fachet, Francois Lallemend, Igor Adameyko, Saida Hadjab, and Edouard B Hannezo. “Theory of Branching Morphogenesis by Local Interactions and Global Guidance.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-27135-5\">https://doi.org/10.1038/s41467-021-27135-5</a>.","mla":"Ucar, Mehmet C., et al. “Theory of Branching Morphogenesis by Local Interactions and Global Guidance.” <i>Nature Communications</i>, vol. 12, 6830, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-27135-5\">10.1038/s41467-021-27135-5</a>.","short":"M.C. Ucar, D. Kamenev, K. Sunadome, D.C. Fachet, F. Lallemend, I. Adameyko, S. Hadjab, E.B. Hannezo, Nature Communications 12 (2021).","ieee":"M. C. Ucar <i>et al.</i>, “Theory of branching morphogenesis by local interactions and global guidance,” <i>Nature Communications</i>, vol. 12. Springer Nature, 2021.","ama":"Ucar MC, Kamenev D, Sunadome K, et al. Theory of branching morphogenesis by local interactions and global guidance. <i>Nature Communications</i>. 2021;12. doi:<a href=\"https://doi.org/10.1038/s41467-021-27135-5\">10.1038/s41467-021-27135-5</a>","ista":"Ucar MC, Kamenev D, Sunadome K, Fachet DC, Lallemend F, Adameyko I, Hadjab S, Hannezo EB. 2021. Theory of branching morphogenesis by local interactions and global guidance. Nature Communications. 12, 6830."},"day":"24","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"date_updated":"2025-04-14T07:43:47Z","publisher":"Springer Nature","department":[{"_id":"EdHa"}],"date_published":"2021-11-24T00:00:00Z","language":[{"iso":"eng"}],"month":"11","file_date_updated":"2021-12-10T08:54:09Z","oa":1,"isi":1,"scopus_import":"1","_id":"10402","type":"journal_article","acknowledgement":"We thank all members of our respective groups for helpful discussion on the paper. The authors are also grateful to Prof. Abdel El. Manira for support and sharing Tg(HUC:Gal4;UAS:Synaptohysin-GFP), to Haohao Wu for discussion, and thank Elena Zabalueva for the zebrafish schematic. The authors also acknowledge Zebrafish core facility, Genome Engineering Zebrafish and Biomedicum Imaging Core from the Karolinska Institutet for technical support. This work received funding from the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 851288 to E.H.) and under the Marie Skłodowska-Curie grant agreement No. 754411 (to M.C.U.); Swedish Research Council (to F.L., I.A. and S.H.); Knut and Alice Wallenberg Foundation (F.L. and I.A.); Swedish Brain Foundation (F.L. and S.H.); Ming Wai Lau Foundation (to F.L.); StratRegen (to F.L.); ERC Consolidator grant STEMMING-FROM-NERVE and ERC Synergy Grant KILL-OR-DIFFERENTIATE (to I.A.); Bertil Hallsten Research Foundation (to I.A.); Cancerfonden (to I.A.); the Paradifference Foundation (to I.A.); Austrian Science Fund (to I.A.); and StratNeuro (to S.H.).","intvolume":"        12","oa_version":"Published Version","article_type":"original","ddc":["573"],"has_accepted_license":"1","quality_controlled":"1","file":[{"success":1,"creator":"cchlebak","date_created":"2021-12-10T08:54:09Z","file_name":"2021_NatComm_Ucar.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"63c56ec75314a71e63e7dd2920b3c5b5","file_size":2303405,"date_updated":"2021-12-10T08:54:09Z","file_id":"10529"}],"publication":"Nature Communications","publication_identifier":{"eissn":["2041-1723"]},"doi":"10.1038/s41467-021-27135-5","article_number":"6830","date_created":"2021-12-05T23:01:40Z","year":"2021","title":"Theory of branching morphogenesis by local interactions and global guidance","publication_status":"published","external_id":{"pmid":["34819507"],"isi":["000722322900020"]},"abstract":[{"lang":"eng","text":"Branching morphogenesis governs the formation of many organs such as lung, kidney, and the neurovascular system. Many studies have explored system-specific molecular and cellular regulatory mechanisms, as well as self-organizing rules underlying branching morphogenesis. However, in addition to local cues, branched tissue growth can also be influenced by global guidance. Here, we develop a theoretical framework for a stochastic self-organized branching process in the presence of external cues. Combining analytical theory with numerical simulations, we predict differential signatures of global vs. local regulatory mechanisms on the branching pattern, such as angle distributions, domain size, and space-filling efficiency. We find that branch alignment follows a generic scaling law determined by the strength of global guidance, while local interactions influence the tissue density but not its overall territory. Finally, using zebrafish innervation as a model system, we test these key features of the model experimentally. Our work thus provides quantitative predictions to disentangle the role of different types of cues in shaping branched structures across scales."}],"article_processing_charge":"No","pmid":1,"related_material":{"record":[{"id":"13058","relation":"research_data","status":"public"}]},"volume":12,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Mehmet C","last_name":"Ucar","id":"50B2A802-6007-11E9-A42B-EB23E6697425","orcid":"0000-0003-0506-4217","full_name":"Ucar, Mehmet C"},{"last_name":"Kamenev","first_name":"Dmitrii","full_name":"Kamenev, Dmitrii"},{"first_name":"Kazunori","last_name":"Sunadome","full_name":"Sunadome, Kazunori"},{"last_name":"Fachet","first_name":"Dominik C","full_name":"Fachet, Dominik C","id":"14FDD550-AA41-11E9-A0E5-1ACCE5697425"},{"last_name":"Lallemend","first_name":"Francois","full_name":"Lallemend, Francois"},{"first_name":"Igor","last_name":"Adameyko","full_name":"Adameyko, Igor"},{"full_name":"Hadjab, Saida","last_name":"Hadjab","first_name":"Saida"},{"last_name":"Hannezo","first_name":"Edouard B","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"}]},{"status":"public","day":"22","citation":{"chicago":"Munjal, Akankshi, Edouard B Hannezo, Tony Y.C. Tsai, Timothy J. Mitchison, and Sean G. Megason. “Extracellular Hyaluronate Pressure Shaped by Cellular Tethers Drives Tissue Morphogenesis.” <i>Cell</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.cell.2021.11.025\">https://doi.org/10.1016/j.cell.2021.11.025</a>.","apa":"Munjal, A., Hannezo, E. B., Tsai, T. Y. C., Mitchison, T. J., &#38; Megason, S. G. (2021). Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2021.11.025\">https://doi.org/10.1016/j.cell.2021.11.025</a>","mla":"Munjal, Akankshi, et al. “Extracellular Hyaluronate Pressure Shaped by Cellular Tethers Drives Tissue Morphogenesis.” <i>Cell</i>, vol. 184, no. 26, Elsevier, 2021, p. 6313–6325.e18, doi:<a href=\"https://doi.org/10.1016/j.cell.2021.11.025\">10.1016/j.cell.2021.11.025</a>.","short":"A. Munjal, E.B. Hannezo, T.Y.C. Tsai, T.J. Mitchison, S.G. Megason, Cell 184 (2021) 6313–6325.e18.","ieee":"A. Munjal, E. B. Hannezo, T. Y. C. Tsai, T. J. Mitchison, and S. G. Megason, “Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis,” <i>Cell</i>, vol. 184, no. 26. Elsevier, p. 6313–6325.e18, 2021.","ista":"Munjal A, Hannezo EB, Tsai TYC, Mitchison TJ, Megason SG. 2021. Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis. Cell. 184(26), 6313–6325.e18.","ama":"Munjal A, Hannezo EB, Tsai TYC, Mitchison TJ, Megason SG. Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis. <i>Cell</i>. 2021;184(26):6313-6325.e18. doi:<a href=\"https://doi.org/10.1016/j.cell.2021.11.025\">10.1016/j.cell.2021.11.025</a>"},"type":"journal_article","acknowledgement":"We thank Ian Swinburne, Sandy Nandagopal, and Toru Kawanishi for support, discussions, and reagents. We thank Vanessa Barone, Joseph Nasser, and members of the Megason lab for useful comments on the manuscript and general feedback. We are grateful to the Heisenberg and Knaut labs for transgenic fish. Diagrams on the right in the graphical abstract were created using BioRender. This work was supported by NIH R01DC015478 and NIH R01GM107733 to S.G.M. A.M. was supported by Human Frontiers Science Program LTF and NIH K99HD098918.","oa_version":"Preprint","intvolume":"       184","article_type":"original","scopus_import":"1","_id":"10573","oa":1,"isi":1,"date_updated":"2025-05-14T11:26:20Z","publisher":"Elsevier","department":[{"_id":"EdHa"}],"date_published":"2021-12-22T00:00:00Z","language":[{"iso":"eng"}],"month":"12","date_created":"2021-12-26T23:01:26Z","year":"2021","publication":"Cell","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"doi":"10.1016/j.cell.2021.11.025","issue":"26","quality_controlled":"1","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2020.09.28.316042","open_access":"1"}],"volume":184,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Akankshi","last_name":"Munjal","full_name":"Munjal, Akankshi"},{"orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","last_name":"Hannezo","first_name":"Edouard B"},{"first_name":"Tony Y.C.","last_name":"Tsai","full_name":"Tsai, Tony Y.C."},{"first_name":"Timothy J.","last_name":"Mitchison","full_name":"Mitchison, Timothy J."},{"first_name":"Sean G.","last_name":"Megason","full_name":"Megason, Sean G."}],"external_id":{"isi":["000735387500002"]},"publication_status":"published","abstract":[{"text":"How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes uridine 5′-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3), drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering.","lang":"eng"}],"article_processing_charge":"No","page":"6313-6325.e18","title":"Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis"},{"article_number":"e60916","date_created":"2021-03-14T23:01:34Z","year":"2021","publication":"eLife","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.60916","quality_controlled":"1","file":[{"success":1,"creator":"dernst","date_created":"2021-03-22T08:50:33Z","file_name":"2021_eLife_Hankeova.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"20ccf4dfe46c48cf986794c8bf4fd1cb","date_updated":"2021-03-22T08:50:33Z","file_size":9259690,"file_id":"9271"}],"ddc":["570"],"has_accepted_license":"1","volume":10,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","author":[{"full_name":"Hankeova, Simona","first_name":"Simona","last_name":"Hankeova"},{"full_name":"Salplachta, Jakub","last_name":"Salplachta","first_name":"Jakub"},{"full_name":"Zikmund, Tomas","first_name":"Tomas","last_name":"Zikmund"},{"full_name":"Kavkova, Michaela","first_name":"Michaela","last_name":"Kavkova"},{"full_name":"Van Hul, Noémi","first_name":"Noémi","last_name":"Van Hul"},{"last_name":"Brinek","first_name":"Adam","full_name":"Brinek, Adam"},{"full_name":"Smekalova, Veronika","first_name":"Veronika","last_name":"Smekalova"},{"first_name":"Jakub","last_name":"Laznovsky","full_name":"Laznovsky, Jakub"},{"full_name":"Dawit, Feven","first_name":"Feven","last_name":"Dawit"},{"full_name":"Jaros, Josef","last_name":"Jaros","first_name":"Josef"},{"full_name":"Bryja, Vítězslav","first_name":"Vítězslav","last_name":"Bryja"},{"last_name":"Lendahl","first_name":"Urban","full_name":"Lendahl, Urban"},{"last_name":"Ellis","first_name":"Ewa","full_name":"Ellis, Ewa"},{"first_name":"Antal","last_name":"Nemeth","full_name":"Nemeth, Antal"},{"last_name":"Fischler","first_name":"Björn","full_name":"Fischler, Björn"},{"last_name":"Hannezo","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B"},{"full_name":"Kaiser, Jozef","first_name":"Jozef","last_name":"Kaiser"},{"full_name":"Andersson, Emma Rachel","first_name":"Emma Rachel","last_name":"Andersson"}],"pmid":1,"publication_status":"published","external_id":{"isi":["000625357100001"],"pmid":["33635272"]},"abstract":[{"text":"Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models.","lang":"eng"}],"article_processing_charge":"No","title":"DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"day":"26","status":"public","project":[{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020"}],"citation":{"mla":"Hankeova, Simona, et al. “DUCT Reveals Architectural Mechanisms Contributing to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” <i>ELife</i>, vol. 10, e60916, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.60916\">10.7554/eLife.60916</a>.","chicago":"Hankeova, Simona, Jakub Salplachta, Tomas Zikmund, Michaela Kavkova, Noémi Van Hul, Adam Brinek, Veronika Smekalova, et al. “DUCT Reveals Architectural Mechanisms Contributing to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.60916\">https://doi.org/10.7554/eLife.60916</a>.","apa":"Hankeova, S., Salplachta, J., Zikmund, T., Kavkova, M., Van Hul, N., Brinek, A., … Andersson, E. R. (2021). DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.60916\">https://doi.org/10.7554/eLife.60916</a>","ista":"Hankeova S, Salplachta J, Zikmund T, Kavkova M, Van Hul N, Brinek A, Smekalova V, Laznovsky J, Dawit F, Jaros J, Bryja V, Lendahl U, Ellis E, Nemeth A, Fischler B, Hannezo EB, Kaiser J, Andersson ER. 2021. DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. eLife. 10, e60916.","ama":"Hankeova S, Salplachta J, Zikmund T, et al. DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.60916\">10.7554/eLife.60916</a>","ieee":"S. Hankeova <i>et al.</i>, “DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","short":"S. Hankeova, J. Salplachta, T. Zikmund, M. Kavkova, N. Van Hul, A. Brinek, V. Smekalova, J. Laznovsky, F. Dawit, J. Jaros, V. Bryja, U. Lendahl, E. Ellis, A. Nemeth, B. Fischler, E.B. Hannezo, J. Kaiser, E.R. Andersson, ELife 10 (2021)."},"type":"journal_article","acknowledgement":"Work in ERA lab is supported by the Swedish Research Council, the Center of Innovative Medicine (CIMED) Grant, Karolinska Institutet, and the Heart and Lung Foundation, and\r\nthe Daniel Alagille Award from the European Association for the Study of the Liver. One project in ERA lab is funded by ModeRNA, unrelated to this project. The funders have no role in the design or interpretation of the work. SH has been supported by a KI-MU PhD student program, and by a Wera Ekstro¨m Foundation Scholarship. We are grateful for support from Tornspiran foundation to NVH. JK: This research was carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II and CzechNanoLab Research Infrastructure supported by MEYS CR (LM2018110) . UL: The financial support from the Swedish Research Council and ICMC (Integrated CardioMetabolic Center) is acknowledged. JJ: The work was supported by the Grant Agency of Masaryk University (project no. MUNI/A/1565/2018). We thank Kari Huppert and Stacey Huppert for their expertise and help regarding bile duct cannulation and their laboratory hospitality. We also thank Nadja Schultz and Charlotte L Mattsson for their help with common bile duct cannulation. We thank Daniel Holl for his help with trachea cannulation. We thank Nikos Papadogiannakis for his assistance with mild Alagille biopsy samples and discussion. We thank Karolinska Biomedicum Imaging Core, especially Shigeaki Kanatani for his help with image analysis. We thank Jan Masek and Carolina Gutierrez for their scientific input in manuscript writing. We thank Peter Ranefall and the BioImage Informatics (SciLife national facility) for their help writing parts of the MATLAB pipeline.\r\nThe TROMA-III antibody developed by Rolf Kemler was obtained from the Developmental Studies Hybridoma (DSHB) Bank developed under the auspices of NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA52242. We thank Goncalo M Brito for all illustrations. This work was supported by the European Union (European Research Council Starting grant 851288 to E.H.).","oa_version":"Published Version","intvolume":"        10","article_type":"original","scopus_import":"1","_id":"9244","file_date_updated":"2021-03-22T08:50:33Z","oa":1,"isi":1,"date_updated":"2026-04-02T14:00:00Z","publisher":"eLife Sciences Publications","department":[{"_id":"EdHa"}],"date_published":"2021-02-26T00:00:00Z","language":[{"iso":"eng"}],"month":"02"},{"article_processing_charge":"No","publication_status":"published","external_id":{"isi":["000663160600002"],"pmid":["33740033"]},"abstract":[{"text":"Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways.","lang":"eng"}],"title":"Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation","author":[{"first_name":"Ulrich","last_name":"Dobramysl","full_name":"Dobramysl, Ulrich"},{"full_name":"Jarsch, Iris Katharina","first_name":"Iris Katharina","last_name":"Jarsch"},{"full_name":"Inoue, Yoshiko","first_name":"Yoshiko","last_name":"Inoue"},{"full_name":"Shimo, Hanae","last_name":"Shimo","first_name":"Hanae"},{"last_name":"Richier","first_name":"Benjamin","full_name":"Richier, Benjamin"},{"full_name":"Gadsby, Jonathan R.","last_name":"Gadsby","first_name":"Jonathan R."},{"last_name":"Mason","first_name":"Julia","full_name":"Mason, Julia"},{"full_name":"Szałapak, Alicja","first_name":"Alicja","last_name":"Szałapak"},{"first_name":"Pantelis Savvas","last_name":"Ioannou","full_name":"Ioannou, Pantelis Savvas"},{"last_name":"Correia","first_name":"Guilherme Pereira","full_name":"Correia, Guilherme Pereira"},{"first_name":"Astrid","last_name":"Walrant","full_name":"Walrant, Astrid"},{"last_name":"Butler","first_name":"Richard","full_name":"Butler, Richard"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","first_name":"Edouard B","last_name":"Hannezo"},{"full_name":"Simons, Benjamin D.","first_name":"Benjamin D.","last_name":"Simons"},{"full_name":"Gallop, Jennifer L.","first_name":"Jennifer L.","last_name":"Gallop"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","volume":220,"pmid":1,"quality_controlled":"1","file":[{"success":1,"creator":"dernst","file_name":"2021_JCB_Dobramysl.pdf","content_type":"application/pdf","date_created":"2021-04-06T10:39:08Z","file_size":9019720,"date_updated":"2021-04-06T10:39:08Z","access_level":"open_access","checksum":"4739ffd90f2c7e05ac5b00f057c58aa2","relation":"main_file","file_id":"9310"}],"has_accepted_license":"1","ddc":["576"],"date_created":"2021-04-04T22:01:21Z","year":"2021","article_number":"e202003052","publication_identifier":{"eissn":["1540-8140"]},"doi":"10.1083/jcb.202003052","issue":"4","publication":"Journal of Cell Biology","isi":1,"file_date_updated":"2021-04-06T10:39:08Z","oa":1,"date_published":"2021-03-19T00:00:00Z","month":"03","language":[{"iso":"eng"}],"date_updated":"2026-04-02T13:59:43Z","department":[{"_id":"EdHa"}],"publisher":"Rockefeller University Press","oa_version":"Published Version","intvolume":"       220","article_type":"original","acknowledgement":"This work was supported by European Research Council grant 281971, Wellcome Trust Research Career Development Fellowship WT095829AIA and Wellcome Trust Senior Research\r\nFellowship 219482/Z/19/Z to J.L. Gallop, a Wellcome Trust Senior Investigator Award 098357 to B.D. Simons, and an Austrian Science Fund grant (P31639) to E. Hannezo. We acknowledge\r\ncore funding by the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492). U. Dobramysl was supported by a Wellcome Trust Junior Interdisciplinary Fellowship grant\r\n(105602/Z/14/Z) and a Herchel Smith Postdoctoral Fellowship. H. Shimo was supported by a Funai Foundation Overseas scholarship.","type":"journal_article","scopus_import":"1","_id":"9306","citation":{"ama":"Dobramysl U, Jarsch IK, Inoue Y, et al. Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation. <i>Journal of Cell Biology</i>. 2021;220(4). doi:<a href=\"https://doi.org/10.1083/jcb.202003052\">10.1083/jcb.202003052</a>","ista":"Dobramysl U, Jarsch IK, Inoue Y, Shimo H, Richier B, Gadsby JR, Mason J, Szałapak A, Ioannou PS, Correia GP, Walrant A, Butler R, Hannezo EB, Simons BD, Gallop JL. 2021. Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation. Journal of Cell Biology. 220(4), e202003052.","ieee":"U. Dobramysl <i>et al.</i>, “Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation,” <i>Journal of Cell Biology</i>, vol. 220, no. 4. Rockefeller University Press, 2021.","short":"U. Dobramysl, I.K. Jarsch, Y. Inoue, H. Shimo, B. Richier, J.R. Gadsby, J. Mason, A. Szałapak, P.S. Ioannou, G.P. Correia, A. Walrant, R. Butler, E.B. Hannezo, B.D. Simons, J.L. Gallop, Journal of Cell Biology 220 (2021).","mla":"Dobramysl, Ulrich, et al. “Stochastic Combinations of Actin Regulatory Proteins Are Sufficient to Drive Filopodia Formation.” <i>Journal of Cell Biology</i>, vol. 220, no. 4, e202003052, Rockefeller University Press, 2021, doi:<a href=\"https://doi.org/10.1083/jcb.202003052\">10.1083/jcb.202003052</a>.","chicago":"Dobramysl, Ulrich, Iris Katharina Jarsch, Yoshiko Inoue, Hanae Shimo, Benjamin Richier, Jonathan R. Gadsby, Julia Mason, et al. “Stochastic Combinations of Actin Regulatory Proteins Are Sufficient to Drive Filopodia Formation.” <i>Journal of Cell Biology</i>. Rockefeller University Press, 2021. <a href=\"https://doi.org/10.1083/jcb.202003052\">https://doi.org/10.1083/jcb.202003052</a>.","apa":"Dobramysl, U., Jarsch, I. K., Inoue, Y., Shimo, H., Richier, B., Gadsby, J. R., … Gallop, J. L. (2021). Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation. <i>Journal of Cell Biology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1083/jcb.202003052\">https://doi.org/10.1083/jcb.202003052</a>"},"project":[{"grant_number":"P31639","_id":"268294B6-B435-11E9-9278-68D0E5697425","name":"Active mechano-chemical description of the cell cytoskeleton","call_identifier":"FWF"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","day":"19"},{"issue":"7","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"doi":"10.1016/j.cell.2021.02.017","publication":"Cell","year":"2021","date_created":"2021-04-11T22:01:14Z","has_accepted_license":"1","ddc":["570"],"corr_author":"1","file":[{"file_id":"9534","file_size":11405875,"date_updated":"2021-06-08T10:04:10Z","checksum":"1e5295fbd9c2a459173ec45a0e8a7c2e","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2021_Cell_Petridou.pdf","date_created":"2021-06-08T10:04:10Z","creator":"cziletti","success":1}],"quality_controlled":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/embryonic-tissue-undergoes-phase-transition/"}]},"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"orcid":"0000-0002-8451-1195","id":"2A003F6C-F248-11E8-B48F-1D18A9856A87","full_name":"Petridou, Nicoletta","last_name":"Petridou","first_name":"Nicoletta"},{"id":"43BE2298-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9806-5643","full_name":"Corominas-Murtra, Bernat","first_name":"Bernat","last_name":"Corominas-Murtra"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"},{"full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","last_name":"Hannezo","first_name":"Edouard B"}],"volume":184,"title":"Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions","page":"1914-1928.e19","article_processing_charge":"No","abstract":[{"lang":"eng","text":"Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin to phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context."}],"external_id":{"isi":["000636734000022"],"pmid":["33730596"]},"publication_status":"published","status":"public","day":"01","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"citation":{"short":"N. Petridou, B. Corominas-Murtra, C.-P.J. Heisenberg, E.B. Hannezo, Cell 184 (2021) 1914–1928.e19.","ieee":"N. Petridou, B. Corominas-Murtra, C.-P. J. Heisenberg, and E. B. Hannezo, “Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions,” <i>Cell</i>, vol. 184, no. 7. Elsevier, p. 1914–1928.e19, 2021.","ama":"Petridou N, Corominas-Murtra B, Heisenberg C-PJ, Hannezo EB. Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions. <i>Cell</i>. 2021;184(7):1914-1928.e19. doi:<a href=\"https://doi.org/10.1016/j.cell.2021.02.017\">10.1016/j.cell.2021.02.017</a>","ista":"Petridou N, Corominas-Murtra B, Heisenberg C-PJ, Hannezo EB. 2021. Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions. Cell. 184(7), 1914–1928.e19.","apa":"Petridou, N., Corominas-Murtra, B., Heisenberg, C.-P. J., &#38; Hannezo, E. B. (2021). Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2021.02.017\">https://doi.org/10.1016/j.cell.2021.02.017</a>","chicago":"Petridou, Nicoletta, Bernat Corominas-Murtra, Carl-Philipp J Heisenberg, and Edouard B Hannezo. “Rigidity Percolation Uncovers a Structural Basis for Embryonic Tissue Phase Transitions.” <i>Cell</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.cell.2021.02.017\">https://doi.org/10.1016/j.cell.2021.02.017</a>.","mla":"Petridou, Nicoletta, et al. “Rigidity Percolation Uncovers a Structural Basis for Embryonic Tissue Phase Transitions.” <i>Cell</i>, vol. 184, no. 7, Elsevier, 2021, p. 1914–1928.e19, doi:<a href=\"https://doi.org/10.1016/j.cell.2021.02.017\">10.1016/j.cell.2021.02.017</a>."},"project":[{"_id":"260F1432-B435-11E9-9278-68D0E5697425","grant_number":"742573","call_identifier":"H2020","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"},{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","grant_number":"851288","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis"},{"grant_number":"V00736","_id":"2693FD8C-B435-11E9-9278-68D0E5697425","name":"Tissue material properties in embryonic development","call_identifier":"FWF"}],"_id":"9316","scopus_import":"1","article_type":"original","oa_version":"Published Version","intvolume":"       184","acknowledgement":"We thank Carl Goodrich and the members of the Heisenberg and Hannezo groups, in particular Reka Korei, for help, technical advice, and discussions; and the Bioimaging and zebrafish facilities of the IST Austria for continuous support. This work was supported by the Elise Richter Program of Austrian Science Fund (FWF) to N.I.P. ( V 736-B26 ) and the European Union (European Research Council Advanced Grant 742573 to C.-P.H. and European Research Council Starting Grant 851288 to E.H.).","type":"journal_article","month":"04","language":[{"iso":"eng"}],"date_published":"2021-04-01T00:00:00Z","publisher":"Elsevier","department":[{"_id":"CaHe"},{"_id":"EdHa"}],"date_updated":"2025-07-10T12:01:42Z","isi":1,"oa":1,"file_date_updated":"2021-06-08T10:04:10Z"},{"ec_funded":1,"day":"21","status":"public","citation":{"chicago":"Yang, Qiutan, Shi-lei Xue, Chii Jou Chan, Markus Rempfler, Dario Vischi, Francisca Maurer-Gutierrez, Takashi Hiiragi, Edouard B Hannezo, and Prisca Liberali. “Cell Fate Coordinates Mechano-Osmotic Forces in Intestinal Crypt Formation.” <i>Nature Cell Biology</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41556-021-00700-2\">https://doi.org/10.1038/s41556-021-00700-2</a>.","apa":"Yang, Q., Xue, S., Chan, C. J., Rempfler, M., Vischi, D., Maurer-Gutierrez, F., … Liberali, P. (2021). Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41556-021-00700-2\">https://doi.org/10.1038/s41556-021-00700-2</a>","mla":"Yang, Qiutan, et al. “Cell Fate Coordinates Mechano-Osmotic Forces in Intestinal Crypt Formation.” <i>Nature Cell Biology</i>, vol. 23, Springer Nature, 2021, pp. 733–744, doi:<a href=\"https://doi.org/10.1038/s41556-021-00700-2\">10.1038/s41556-021-00700-2</a>.","short":"Q. Yang, S. Xue, C.J. Chan, M. Rempfler, D. Vischi, F. Maurer-Gutierrez, T. Hiiragi, E.B. Hannezo, P. Liberali, Nature Cell Biology 23 (2021) 733–744.","ieee":"Q. Yang <i>et al.</i>, “Cell fate coordinates mechano-osmotic forces in intestinal crypt formation,” <i>Nature Cell Biology</i>, vol. 23. Springer Nature, pp. 733–744, 2021.","ama":"Yang Q, Xue S, Chan CJ, et al. Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. <i>Nature Cell Biology</i>. 2021;23:733–744. doi:<a href=\"https://doi.org/10.1038/s41556-021-00700-2\">10.1038/s41556-021-00700-2</a>","ista":"Yang Q, Xue S, Chan CJ, Rempfler M, Vischi D, Maurer-Gutierrez F, Hiiragi T, Hannezo EB, Liberali P. 2021. Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. Nature Cell Biology. 23, 733–744."},"project":[{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","call_identifier":"H2020"},{"name":"Active mechano-chemical description of the cell cytoskeleton","call_identifier":"FWF","grant_number":"P31639","_id":"268294B6-B435-11E9-9278-68D0E5697425"}],"article_type":"original","oa_version":"Preprint","intvolume":"        23","type":"journal_article","acknowledgement":"We acknowledge the members of the Lennon-Duménil laboratory for sharing the mouse line of Myh9-GFP. We are grateful to the members of the Liberali laboratory and the FMI facilities for their support. We thank E. Tagliavini for IT support; L. Gelman for assistance and training; S. Bichet and A. Bogucki for helping with histology of mouse tissues; H. Kohler for fluorescence-activated cell sorting; G. Q. G. de Medeiros for maintenance of light-sheet microscopy; M. G. Stadler for scRNA-seq analysis; G. Gay for discussions on the 3D vertex model; the members of the Liberali laboratory, C. P. Heisenberg and C. Tsiairis for reading and providing feedback on the manuscript. Funding: Q.Y. is supported by a Postdoc fellowship from Peter und Taul Engelhorn Stiftung (PTES). This work received funding from the European Research Council (ERC) under the EU Horizon 2020 research and Innovation Programme Grant Agreement no. 758617 (to P.L.), the Swiss National Foundation (SNF) (POOP3_157531, to P.L.) and from the ERC under the EU Horizon 2020 Research and Innovation Program Grant Agreements 851288 (to E.H.) and the Austrian Science Fund (FWF) (P31639, to E.H.).","_id":"9629","scopus_import":"1","isi":1,"oa":1,"month":"06","language":[{"iso":"eng"}],"date_published":"2021-06-21T00:00:00Z","department":[{"_id":"EdHa"}],"publisher":"Springer Nature","date_updated":"2025-04-14T07:52:26Z","year":"2021","date_created":"2021-07-04T22:01:25Z","doi":"10.1038/s41556-021-00700-2","publication_identifier":{"issn":["1465-7392"],"eissn":["1476-4679"]},"publication":"Nature Cell Biology","corr_author":"1","quality_controlled":"1","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2020.05.13.094359","open_access":"1"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Yang, Qiutan","last_name":"Yang","first_name":"Qiutan"},{"first_name":"Shi-lei","last_name":"Xue","id":"31D2C804-F248-11E8-B48F-1D18A9856A87","full_name":"Xue, Shi-lei"},{"full_name":"Chan, Chii Jou","last_name":"Chan","first_name":"Chii Jou"},{"full_name":"Rempfler, Markus","first_name":"Markus","last_name":"Rempfler"},{"full_name":"Vischi, Dario","first_name":"Dario","last_name":"Vischi"},{"last_name":"Maurer-Gutierrez","first_name":"Francisca","full_name":"Maurer-Gutierrez, Francisca"},{"full_name":"Hiiragi, Takashi","last_name":"Hiiragi","first_name":"Takashi"},{"first_name":"Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B"},{"full_name":"Liberali, Prisca","last_name":"Liberali","first_name":"Prisca"}],"volume":23,"pmid":1,"page":"733–744","article_processing_charge":"No","abstract":[{"lang":"eng","text":"Intestinal organoids derived from single cells undergo complex crypt–villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis."}],"publication_status":"published","external_id":{"isi":["000664016300003"],"pmid":["34155381"]},"title":"Cell fate coordinates mechano-osmotic forces in intestinal crypt formation"},{"file_date_updated":"2021-08-23T07:32:20Z","oa":1,"isi":1,"date_updated":"2025-07-10T12:02:07Z","department":[{"_id":"EdHa"}],"publisher":"The Company of Biologists","date_published":"2021-07-01T00:00:00Z","month":"07","language":[{"iso":"eng"}],"acknowledgement":"We would like to thank the entire Paluch and Baum laboratories at the MRC-LMCB and the Chalut lab at the Cambridge SCI for discussions and feedback throughout the project, and the MRC-LMCB microscopy platform, in particular Andrew Vaughan, for technical support.","type":"journal_article","intvolume":"       134","oa_version":"Published Version","article_type":"original","scopus_import":"1","_id":"9952","citation":{"ista":"Chaigne A, Smith MB, Cavestany RL, Hannezo EB, Chalut KJ, Paluch EK. 2021. Three-dimensional geometry controls division symmetry in stem cell colonies. Journal of Cell Science. 134(14), jcs255018.","ama":"Chaigne A, Smith MB, Cavestany RL, Hannezo EB, Chalut KJ, Paluch EK. Three-dimensional geometry controls division symmetry in stem cell colonies. <i>Journal of Cell Science</i>. 2021;134(14). doi:<a href=\"https://doi.org/10.1242/jcs.255018\">10.1242/jcs.255018</a>","short":"A. Chaigne, M.B. Smith, R.L. Cavestany, E.B. Hannezo, K.J. Chalut, E.K. Paluch, Journal of Cell Science 134 (2021).","ieee":"A. Chaigne, M. B. Smith, R. L. Cavestany, E. B. Hannezo, K. J. Chalut, and E. K. Paluch, “Three-dimensional geometry controls division symmetry in stem cell colonies,” <i>Journal of Cell Science</i>, vol. 134, no. 14. The Company of Biologists, 2021.","mla":"Chaigne, Agathe, et al. “Three-Dimensional Geometry Controls Division Symmetry in Stem Cell Colonies.” <i>Journal of Cell Science</i>, vol. 134, no. 14, jcs255018, The Company of Biologists, 2021, doi:<a href=\"https://doi.org/10.1242/jcs.255018\">10.1242/jcs.255018</a>.","apa":"Chaigne, A., Smith, M. B., Cavestany, R. L., Hannezo, E. B., Chalut, K. J., &#38; Paluch, E. K. (2021). Three-dimensional geometry controls division symmetry in stem cell colonies. <i>Journal of Cell Science</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/jcs.255018\">https://doi.org/10.1242/jcs.255018</a>","chicago":"Chaigne, Agathe, Matthew B. Smith, R. L. Cavestany, Edouard B Hannezo, Kevin J. Chalut, and Ewa K. Paluch. “Three-Dimensional Geometry Controls Division Symmetry in Stem Cell Colonies.” <i>Journal of Cell Science</i>. The Company of Biologists, 2021. <a href=\"https://doi.org/10.1242/jcs.255018\">https://doi.org/10.1242/jcs.255018</a>."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","day":"01","external_id":{"isi":["000681395800008"]},"publication_status":"published","abstract":[{"text":"Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in two-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA (also known as NUMA1) orient division along the interphase long axis of the cell. However, little is known about how cells control spindle positioning in three-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Here, we use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate division in 3D. We observe that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell–cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry.","lang":"eng"}],"article_processing_charge":"Yes (in subscription journal)","title":"Three-dimensional geometry controls division symmetry in stem cell colonies","volume":134,"author":[{"last_name":"Chaigne","first_name":"Agathe","full_name":"Chaigne, Agathe"},{"first_name":"Matthew B.","last_name":"Smith","full_name":"Smith, Matthew B."},{"last_name":"Cavestany","first_name":"R. L.","full_name":"Cavestany, R. L."},{"full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561","last_name":"Hannezo","first_name":"Edouard B"},{"last_name":"Chalut","first_name":"Kevin J.","full_name":"Chalut, Kevin J."},{"full_name":"Paluch, Ewa K.","first_name":"Ewa K.","last_name":"Paluch"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","file":[{"creator":"asandaue","success":1,"content_type":"application/pdf","file_name":"2021_JournalOfCellScience_Chaigne.pdf","date_created":"2021-08-23T07:32:20Z","date_updated":"2021-08-23T07:32:20Z","file_size":8651724,"relation":"main_file","checksum":"f086f9d7cb63b2474c01921cb060c513","access_level":"open_access","file_id":"9954"}],"ddc":["570"],"has_accepted_license":"1","article_number":"jcs255018","date_created":"2021-08-22T22:01:20Z","year":"2021","publication":"Journal of Cell Science","publication_identifier":{"issn":["0021-9533"],"eissn":["1477-9137"]},"doi":"10.1242/jcs.255018","issue":"14"}]