--- _id: '10705' abstract: - lang: eng 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. 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. article_processing_charge: No article_type: original author: - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Hannezo EB, Heisenberg C-PJ. Rigidity transitions in development and disease. Trends in Cell Biology. 2022;32(5):P433-444. doi:10.1016/j.tcb.2021.12.006 apa: Hannezo, E. B., & Heisenberg, C.-P. J. (2022). Rigidity transitions in development and disease. Trends in Cell Biology. Cell Press. https://doi.org/10.1016/j.tcb.2021.12.006 chicago: Hannezo, Edouard B, and Carl-Philipp J Heisenberg. “Rigidity Transitions in Development and Disease.” Trends in Cell Biology. Cell Press, 2022. https://doi.org/10.1016/j.tcb.2021.12.006. ieee: E. B. Hannezo and C.-P. J. Heisenberg, “Rigidity transitions in development and disease,” Trends in Cell Biology, vol. 32, no. 5. Cell Press, pp. P433-444, 2022. ista: Hannezo EB, Heisenberg C-PJ. 2022. Rigidity transitions in development and disease. Trends in Cell Biology. 32(5), P433-444. mla: Hannezo, Edouard B., and Carl-Philipp J. Heisenberg. “Rigidity Transitions in Development and Disease.” Trends in Cell Biology, vol. 32, no. 5, Cell Press, 2022, pp. P433-444, doi:10.1016/j.tcb.2021.12.006. short: E.B. Hannezo, C.-P.J. Heisenberg, Trends in Cell Biology 32 (2022) P433-444. date_created: 2022-01-30T23:01:34Z date_published: 2022-05-01T00:00:00Z date_updated: 2023-08-02T14:03:53Z day: '01' department: - _id: EdHa - _id: CaHe doi: 10.1016/j.tcb.2021.12.006 external_id: isi: - '000795773900009' pmid: - '35058104' intvolume: ' 32' isi: 1 issue: '5' language: - iso: eng month: '05' oa_version: None page: P433-444 pmid: 1 publication: Trends in Cell Biology publication_identifier: eissn: - 1879-3088 issn: - 0962-8924 publication_status: published publisher: Cell Press quality_controlled: '1' scopus_import: '1' status: public title: Rigidity transitions in development and disease type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 32 year: '2022' ... --- _id: '10825' abstract: - lang: eng 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. 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_processing_charge: No article_type: original author: - first_name: Ayaka full_name: Yanagida, Ayaka last_name: Yanagida - first_name: Elena full_name: Corujo-Simon, Elena last_name: Corujo-Simon - first_name: Christopher K. full_name: Revell, Christopher K. last_name: Revell - first_name: Preeti full_name: Sahu, Preeti id: 55BA52EE-A185-11EA-88FD-18AD3DDC885E last_name: Sahu - first_name: Giuliano G. full_name: Stirparo, Giuliano G. last_name: Stirparo - first_name: Irene M. full_name: Aspalter, Irene M. last_name: Aspalter - first_name: Alex K. full_name: Winkel, Alex K. last_name: Winkel - first_name: Ruby full_name: Peters, Ruby last_name: Peters - first_name: Henry full_name: De Belly, Henry last_name: De Belly - first_name: Davide A.D. full_name: Cassani, Davide A.D. last_name: Cassani - first_name: Sarra full_name: Achouri, Sarra last_name: Achouri - first_name: Raphael full_name: Blumenfeld, Raphael last_name: Blumenfeld - first_name: Kristian full_name: Franze, Kristian last_name: Franze - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Ewa K. full_name: Paluch, Ewa K. last_name: Paluch - first_name: Jennifer full_name: Nichols, Jennifer last_name: Nichols - first_name: Kevin J. full_name: Chalut, Kevin J. last_name: Chalut citation: ama: Yanagida A, Corujo-Simon E, Revell CK, et al. Cell surface fluctuations regulate early embryonic lineage sorting. Cell. 2022;185(5):777-793.e20. doi:10.1016/j.cell.2022.01.022 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. Cell. Cell Press. https://doi.org/10.1016/j.cell.2022.01.022 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.” Cell. Cell Press, 2022. https://doi.org/10.1016/j.cell.2022.01.022. ieee: A. Yanagida et al., “Cell surface fluctuations regulate early embryonic lineage sorting,” Cell, vol. 185, no. 5. Cell Press, p. 777–793.e20, 2022. ista: Yanagida A, Corujo-Simon E, Revell CK, Sahu P, Stirparo GG, Aspalter IM, Winkel AK, Peters R, De Belly H, Cassani DAD, Achouri S, Blumenfeld R, Franze K, Hannezo EB, Paluch EK, Nichols J, Chalut KJ. 2022. Cell surface fluctuations regulate early embryonic lineage sorting. Cell. 185(5), 777–793.e20. mla: Yanagida, Ayaka, et al. “Cell Surface Fluctuations Regulate Early Embryonic Lineage Sorting.” Cell, vol. 185, no. 5, Cell Press, 2022, p. 777–793.e20, doi:10.1016/j.cell.2022.01.022. 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. date_created: 2022-03-06T23:01:52Z date_published: 2022-02-22T00:00:00Z date_updated: 2023-08-02T14:43:50Z day: '22' ddc: - '570' department: - _id: EdHa doi: 10.1016/j.cell.2022.01.022 ec_funded: 1 external_id: isi: - '000796293700007' pmid: - '35196500' file: - access_level: open_access checksum: ae305060e8031297771b89dae9e36a29 content_type: application/pdf creator: dernst date_created: 2022-03-07T07:55:23Z date_updated: 2022-03-07T07:55:23Z file_id: '10831' file_name: 2022_Cell_Yanagida.pdf file_size: 8478995 relation: main_file success: 1 file_date_updated: 2022-03-07T07:55:23Z has_accepted_license: '1' intvolume: ' 185' isi: 1 issue: '5' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '02' oa: 1 oa_version: Published Version page: 777-793.e20 pmid: 1 project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: Cell publication_identifier: eissn: - '10974172' issn: - '00928674' publication_status: published publisher: Cell Press quality_controlled: '1' scopus_import: '1' status: public title: Cell surface fluctuations regulate early embryonic lineage sorting tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 185 year: '2022' ... --- _id: '12209' abstract: - lang: eng 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. acknowledged_ssus: - _id: Bio - _id: LifeSc 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.)." article_processing_charge: No article_type: original author: - first_name: Diana C full_name: Nunes Pinheiro, Diana C id: 2E839F16-F248-11E8-B48F-1D18A9856A87 last_name: Nunes Pinheiro orcid: 0000-0003-4333-7503 - first_name: Roland full_name: Kardos, Roland id: 4039350E-F248-11E8-B48F-1D18A9856A87 last_name: Kardos - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 citation: ama: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. 2022;18(12):1482-1493. doi:10.1038/s41567-022-01787-6 apa: Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., & Heisenberg, C.-P. J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-022-01787-6 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.” Nature Physics. Springer Nature, 2022. https://doi.org/10.1038/s41567-022-01787-6. 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,” Nature Physics, vol. 18, no. 12. Springer Nature, pp. 1482–1493, 2022. 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. mla: Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis via Motility-Driven Unjamming.” Nature Physics, vol. 18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:10.1038/s41567-022-01787-6. short: D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 18 (2022) 1482–1493. date_created: 2023-01-16T09:45:19Z date_published: 2022-12-01T00:00:00Z date_updated: 2023-08-04T09:15:58Z day: '01' ddc: - '570' department: - _id: CaHe - _id: EdHa doi: 10.1038/s41567-022-01787-6 ec_funded: 1 external_id: isi: - '000871319900002' file: - access_level: open_access checksum: c86a8e8d80d1bfc46d56a01e88a2526a content_type: application/pdf creator: dernst date_created: 2023-01-27T07:32:01Z date_updated: 2023-01-27T07:32:01Z file_id: '12412' file_name: 2022_NaturePhysics_Pinheiro.pdf file_size: 36703569 relation: main_file success: 1 file_date_updated: 2023-01-27T07:32:01Z has_accepted_license: '1' intvolume: ' 18' isi: 1 issue: '12' keyword: - General Physics and Astronomy language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 1482-1493 project: - _id: 26520D1E-B435-11E9-9278-68D0E5697425 grant_number: ALTF 850-2017 name: Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation - _id: 26520D1E-B435-11E9-9278-68D0E5697425 grant_number: ALTF 850-2017 name: Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation publication: Nature Physics publication_identifier: eissn: - 1745-2481 issn: - 1745-2473 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 18 year: '2022' ... --- _id: '12217' 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. 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." article_number: '5219' article_processing_charge: No article_type: original author: - first_name: S. full_name: Randriamanantsoa, S. last_name: Randriamanantsoa - first_name: A. full_name: Papargyriou, A. last_name: Papargyriou - first_name: H. C. full_name: Maurer, H. C. last_name: Maurer - first_name: K. full_name: Peschke, K. last_name: Peschke - first_name: M. full_name: Schuster, M. last_name: Schuster - first_name: G. full_name: Zecchin, G. last_name: Zecchin - first_name: K. full_name: Steiger, K. last_name: Steiger - first_name: R. full_name: Öllinger, R. last_name: Öllinger - first_name: D. full_name: Saur, D. last_name: Saur - first_name: C. full_name: Scheel, C. last_name: Scheel - first_name: R. full_name: Rad, R. last_name: Rad - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: M. full_name: Reichert, M. last_name: Reichert - first_name: A. R. full_name: Bausch, A. R. last_name: Bausch citation: ama: Randriamanantsoa S, Papargyriou A, Maurer HC, et al. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. Nature Communications. 2022;13. doi:10.1038/s41467-022-32806-y 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. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32806-y 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.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32806-y. ieee: S. Randriamanantsoa et al., “Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids,” Nature Communications, vol. 13. Springer Nature, 2022. ista: Randriamanantsoa S, Papargyriou A, Maurer HC, Peschke K, Schuster M, Zecchin G, Steiger K, Öllinger R, Saur D, Scheel C, Rad R, Hannezo EB, Reichert M, Bausch AR. 2022. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. Nature Communications. 13, 5219. mla: Randriamanantsoa, S., et al. “Spatiotemporal Dynamics of Self-Organized Branching in Pancreas-Derived Organoids.” Nature Communications, vol. 13, 5219, Springer Nature, 2022, doi:10.1038/s41467-022-32806-y. 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). date_created: 2023-01-16T09:46:53Z date_published: 2022-09-05T00:00:00Z date_updated: 2023-08-04T09:25:23Z day: '05' ddc: - '570' department: - _id: EdHa doi: 10.1038/s41467-022-32806-y ec_funded: 1 external_id: isi: - '000850348400025' file: - access_level: open_access checksum: 295261b5172274fd5b8f85a6a6058828 content_type: application/pdf creator: dernst date_created: 2023-01-27T08:14:48Z date_updated: 2023-01-27T08:14:48Z file_id: '12416' file_name: 2022_NatureCommunications_Randriamanantsoa.pdf file_size: 22645149 relation: main_file success: 1 file_date_updated: 2023-01-27T08:14:48Z has_accepted_license: '1' intvolume: ' 13' isi: 1 keyword: - General Physics and Astronomy - General Biochemistry - Genetics and Molecular Biology - General Chemistry - Multidisciplinary language: - iso: eng month: '09' oa: 1 oa_version: Published Version project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '13068' relation: research_data status: public scopus_import: '1' status: public title: Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2022' ... --- _id: '12253' 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. 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.' article_number: eadd2488 article_processing_charge: No article_type: original author: - first_name: Jessica full_name: Stock, Jessica last_name: Stock - first_name: Tomas full_name: Kazmar, Tomas last_name: Kazmar - first_name: Friederike full_name: Schlumm, Friederike last_name: Schlumm - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Andrea full_name: Pauli, Andrea last_name: Pauli citation: ama: Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. A self-generated Toddler gradient guides mesodermal cell migration. Science Advances. 2022;8(37). doi:10.1126/sciadv.add2488 apa: Stock, J., Kazmar, T., Schlumm, F., Hannezo, E. B., & Pauli, A. (2022). A self-generated Toddler gradient guides mesodermal cell migration. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.add2488 chicago: Stock, Jessica, Tomas Kazmar, Friederike Schlumm, Edouard B Hannezo, and Andrea Pauli. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.” Science Advances. American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.add2488. ieee: J. Stock, T. Kazmar, F. Schlumm, E. B. Hannezo, and A. Pauli, “A self-generated Toddler gradient guides mesodermal cell migration,” Science Advances, vol. 8, no. 37. American Association for the Advancement of Science, 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. mla: Stock, Jessica, et al. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.” Science Advances, vol. 8, no. 37, eadd2488, American Association for the Advancement of Science, 2022, doi:10.1126/sciadv.add2488. short: J. Stock, T. Kazmar, F. Schlumm, E.B. Hannezo, A. Pauli, Science Advances 8 (2022). date_created: 2023-01-16T09:57:10Z date_published: 2022-09-14T00:00:00Z date_updated: 2023-08-04T09:49:59Z day: '14' ddc: - '570' department: - _id: EdHa doi: 10.1126/sciadv.add2488 ec_funded: 1 external_id: isi: - '000888875000009' pmid: - '36103529' file: - access_level: open_access checksum: f59cdb824e5d4221045def81f46f6c65 content_type: application/pdf creator: dernst date_created: 2023-01-30T09:27:49Z date_updated: 2023-01-30T09:27:49Z file_id: '12444' file_name: 2022_ScienceAdvances_Stock.pdf file_size: 1636732 relation: main_file success: 1 file_date_updated: 2023-01-30T09:27:49Z has_accepted_license: '1' intvolume: ' 8' isi: 1 issue: '37' language: - iso: eng month: '09' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: Science Advances publication_identifier: issn: - 2375-2548 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' scopus_import: '1' status: public title: A self-generated Toddler gradient guides mesodermal cell migration tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 8 year: '2022' ... --- _id: '12277' abstract: - lang: eng 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. 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_number: '031041' article_processing_charge: No article_type: original author: - first_name: David full_name: Brückner, David id: e1e86031-6537-11eb-953a-f7ab92be508d last_name: Brückner orcid: 0000-0001-7205-2975 - first_name: Matthew full_name: Schmitt, Matthew last_name: Schmitt - first_name: Alexandra full_name: Fink, Alexandra last_name: Fink - first_name: Georg full_name: Ladurner, Georg last_name: Ladurner - first_name: Johannes full_name: Flommersfeld, Johannes last_name: Flommersfeld - first_name: Nicolas full_name: Arlt, Nicolas last_name: Arlt - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Joachim O. full_name: Rädler, Joachim O. last_name: Rädler - first_name: Chase P. full_name: Broedersz, Chase P. last_name: Broedersz citation: ama: Brückner D, Schmitt M, Fink A, et al. Geometry adaptation of protrusion and polarity dynamics in confined cell migration. Physical Review X. 2022;12(3). doi:10.1103/physrevx.12.031041 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. Physical Review X. American Physical Society. https://doi.org/10.1103/physrevx.12.031041 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.” Physical Review X. American Physical Society, 2022. https://doi.org/10.1103/physrevx.12.031041. ieee: D. Brückner et al., “Geometry adaptation of protrusion and polarity dynamics in confined cell migration,” Physical Review X, 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. mla: Brückner, David, et al. “Geometry Adaptation of Protrusion and Polarity Dynamics in Confined Cell Migration.” Physical Review X, vol. 12, no. 3, 031041, American Physical Society, 2022, doi:10.1103/physrevx.12.031041. 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). date_created: 2023-01-16T10:02:06Z date_published: 2022-09-20T00:00:00Z date_updated: 2023-08-04T10:25:49Z day: '20' ddc: - '530' - '570' department: - _id: EdHa doi: 10.1103/physrevx.12.031041 external_id: arxiv: - '2106.01014' isi: - '000861534700001' file: - access_level: open_access checksum: 40a8fbc3663bf07b37cb80020974d40d content_type: application/pdf creator: dernst date_created: 2023-01-30T11:07:27Z date_updated: 2023-01-30T11:07:27Z file_id: '12458' file_name: 2022_PhysicalReviewX_Brueckner.pdf file_size: 4686804 relation: main_file success: 1 file_date_updated: 2023-01-30T11:07:27Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '3' keyword: - General Physics and Astronomy language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: Physical Review X publication_identifier: issn: - 2160-3308 publication_status: published publisher: American Physical Society quality_controlled: '1' scopus_import: '1' status: public title: Geometry adaptation of protrusion and polarity dynamics in confined cell migration tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2022' ... --- _id: '12274' 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. 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). article_processing_charge: No article_type: original author: - first_name: Maria full_name: Azkanaz, Maria last_name: Azkanaz - first_name: Bernat full_name: Corominas-Murtra, Bernat id: 43BE2298-F248-11E8-B48F-1D18A9856A87 last_name: Corominas-Murtra orcid: 0000-0001-9806-5643 - first_name: Saskia I. J. full_name: Ellenbroek, Saskia I. J. last_name: Ellenbroek - first_name: Lotte full_name: Bruens, Lotte last_name: Bruens - first_name: Anna T. full_name: Webb, Anna T. last_name: Webb - first_name: Dimitrios full_name: Laskaris, Dimitrios last_name: Laskaris - first_name: Koen C. full_name: Oost, Koen C. last_name: Oost - first_name: Simona J. A. full_name: Lafirenze, Simona J. A. last_name: Lafirenze - first_name: Karl full_name: Annusver, Karl last_name: Annusver - first_name: Hendrik A. full_name: Messal, Hendrik A. last_name: Messal - first_name: Sharif full_name: Iqbal, Sharif last_name: Iqbal - first_name: Dustin J. full_name: Flanagan, Dustin J. last_name: Flanagan - first_name: David J. full_name: Huels, David J. last_name: Huels - first_name: Felipe full_name: Rojas-Rodríguez, Felipe last_name: Rojas-Rodríguez - first_name: Miguel full_name: Vizoso, Miguel last_name: Vizoso - first_name: Maria full_name: Kasper, Maria last_name: Kasper - first_name: Owen J. full_name: Sansom, Owen J. last_name: Sansom - first_name: Hugo J. full_name: Snippert, Hugo J. last_name: Snippert - first_name: Prisca full_name: Liberali, Prisca last_name: Liberali - first_name: Benjamin D. full_name: Simons, Benjamin D. last_name: Simons - first_name: Pekka full_name: Katajisto, Pekka last_name: Katajisto - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Jacco full_name: van Rheenen, Jacco last_name: van Rheenen citation: ama: Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, et al. Retrograde movements determine effective stem cell numbers in the intestine. Nature. 2022;607(7919):548-554. doi:10.1038/s41586-022-04962-0 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. Nature. Springer Nature. https://doi.org/10.1038/s41586-022-04962-0 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.” Nature. Springer Nature, 2022. https://doi.org/10.1038/s41586-022-04962-0. ieee: M. Azkanaz et al., “Retrograde movements determine effective stem cell numbers in the intestine,” Nature, vol. 607, no. 7919. Springer Nature, pp. 548–554, 2022. ista: Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, Bruens L, Webb AT, Laskaris D, Oost KC, Lafirenze SJA, Annusver K, Messal HA, Iqbal S, Flanagan DJ, Huels DJ, Rojas-Rodríguez F, Vizoso M, Kasper M, Sansom OJ, Snippert HJ, Liberali P, Simons BD, Katajisto P, Hannezo EB, van Rheenen J. 2022. Retrograde movements determine effective stem cell numbers in the intestine. Nature. 607(7919), 548–554. mla: Azkanaz, Maria, et al. “Retrograde Movements Determine Effective Stem Cell Numbers in the Intestine.” Nature, vol. 607, no. 7919, Springer Nature, 2022, pp. 548–54, doi:10.1038/s41586-022-04962-0. 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. date_created: 2023-01-16T10:01:29Z date_published: 2022-07-13T00:00:00Z date_updated: 2023-10-03T11:16:30Z day: '13' department: - _id: EdHa doi: 10.1038/s41586-022-04962-0 ec_funded: 1 external_id: isi: - '000824430000004' pmid: - '35831497' intvolume: ' 607' isi: 1 issue: '7919' keyword: - Multidisciplinary language: - iso: eng main_file_link: - open_access: '1' url: https://helda.helsinki.fi/items/94433455-4854-45c0-9de8-7326caea8780 month: '07' oa: 1 oa_version: Submitted Version page: 548-554 pmid: 1 project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: Nature publication_identifier: eissn: - 1476-4687 issn: - 0028-0836 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/JaccovanRheenenLab/Retrograde_movement_Azkanaz_Nature_2022 scopus_import: '1' status: public title: Retrograde movements determine effective stem cell numbers in the intestine type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 607 year: '2022' ... --- _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". article_processing_charge: No author: - first_name: Samuel full_name: Randriamanantsoa, Samuel last_name: Randriamanantsoa - first_name: Aristeidis full_name: Papargyriou, Aristeidis last_name: Papargyriou - first_name: Carlo full_name: Maurer, Carlo last_name: Maurer - first_name: Katja full_name: Peschke, Katja last_name: Peschke - first_name: Maximilian full_name: Schuster, Maximilian last_name: Schuster - first_name: Giulia full_name: Zecchin, Giulia last_name: Zecchin - first_name: Katja full_name: Steiger, Katja last_name: Steiger - first_name: Rupert full_name: Öllinger, Rupert last_name: Öllinger - first_name: Dieter full_name: Saur, Dieter last_name: Saur - first_name: Christina full_name: Scheel, Christina last_name: Scheel - first_name: Roland full_name: Rad, Roland last_name: Rad - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Maximilian full_name: Reichert, Maximilian last_name: Reichert - first_name: Andreas R. full_name: Bausch, Andreas R. last_name: Bausch citation: ama: Randriamanantsoa S, Papargyriou A, Maurer C, et al. Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids. 2021. doi:10.5281/ZENODO.5148117 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. https://doi.org/10.5281/ZENODO.5148117 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. https://doi.org/10.5281/ZENODO.5148117. ieee: S. Randriamanantsoa et al., “Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids.” Zenodo, 2021. 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, 10.5281/ZENODO.5148117. mla: Randriamanantsoa, Samuel, et al. Spatiotemporal Dynamics of Self-Organized Branching in Pancreas-Derived Organoids. Zenodo, 2021, doi:10.5281/ZENODO.5148117. 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). date_created: 2023-05-23T16:39:24Z date_published: 2021-07-30T00:00:00Z date_updated: 2023-08-04T09:25:23Z day: '30' ddc: - '570' department: - _id: EdHa doi: 10.5281/ZENODO.5148117 main_file_link: - open_access: '1' url: https://doi.org/10.5281/zenodo.6577226 month: '07' oa: 1 oa_version: Published Version publisher: Zenodo related_material: record: - id: '12217' relation: used_in_publication status: public status: public title: Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: research_data_reference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2021' ... --- _id: '8602' abstract: - lang: eng text: Collective cell migration offers a rich field of study for non-equilibrium physics and cellular biology, revealing phenomena such as glassy dynamics, pattern formation and active turbulence. However, how mechanical and chemical signalling are integrated at the cellular level to give rise to such collective behaviours remains unclear. We address this by focusing on the highly conserved phenomenon of spatiotemporal waves of density and extracellular signal-regulated kinase (ERK) activation, which appear both in vitro and in vivo during collective cell migration and wound healing. First, we propose a biophysical theory, backed by mechanical and optogenetic perturbation experiments, showing that patterns can be quantitatively explained by a mechanochemical coupling between active cellular tensions and the mechanosensitive ERK pathway. Next, we demonstrate how this biophysical mechanism can robustly induce long-ranged order and migration in a desired orientation, and we determine the theoretically optimal wavelength and period for inducing maximal migration towards free edges, which fits well with experimentally observed dynamics. We thereby provide a bridge between the biophysical origin of spatiotemporal instabilities and the design principles of robust and efficient long-ranged migration. acknowledgement: We would like to thank G. Tkacik and all of the members of the Hannezo and Hirashima groups for useful discussions, X. Trepat for help on traction force microscopy and M. Matsuda for use of the lab facility. E.H. acknowledges grants from the Austrian Science Fund (FWF) (P 31639) and the European Research Council (851288). T.H. acknowledges a grant from JST, PRESTO (JPMJPR1949). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 665385 (to D.B.), from JSPS KAKENHI grant no. 17J02107 (to N.H.) and from the SPIRITS 2018 of Kyoto University (to E.H. and T.H.). article_processing_charge: No article_type: original author: - first_name: Daniel R full_name: Boocock, Daniel R id: 453AF628-F248-11E8-B48F-1D18A9856A87 last_name: Boocock orcid: 0000-0002-1585-2631 - first_name: Naoya full_name: Hino, Naoya last_name: Hino - first_name: Natalia full_name: Ruzickova, Natalia id: D2761128-D73D-11E9-A1BF-BA0DE6697425 last_name: Ruzickova - first_name: Tsuyoshi full_name: Hirashima, Tsuyoshi last_name: Hirashima - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 citation: ama: Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics. 2021;17:267-274. doi:10.1038/s41567-020-01037-7 apa: Boocock, D. R., Hino, N., Ruzickova, N., Hirashima, T., & Hannezo, E. B. (2021). Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-020-01037-7 chicago: Boocock, Daniel R, Naoya Hino, Natalia Ruzickova, Tsuyoshi Hirashima, and Edouard B Hannezo. “Theory of Mechanochemical Patterning and Optimal Migration in Cell Monolayers.” Nature Physics. Springer Nature, 2021. https://doi.org/10.1038/s41567-020-01037-7. ieee: D. R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, and E. B. Hannezo, “Theory of mechanochemical patterning and optimal migration in cell monolayers,” Nature Physics, vol. 17. Springer Nature, pp. 267–274, 2021. ista: Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. 2021. Theory of mechanochemical patterning and optimal migration in cell monolayers. Nature Physics. 17, 267–274. mla: Boocock, Daniel R., et al. “Theory of Mechanochemical Patterning and Optimal Migration in Cell Monolayers.” Nature Physics, vol. 17, Springer Nature, 2021, pp. 267–74, doi:10.1038/s41567-020-01037-7. short: D.R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, E.B. Hannezo, Nature Physics 17 (2021) 267–274. date_created: 2020-10-04T22:01:37Z date_published: 2021-02-01T00:00:00Z date_updated: 2023-08-04T11:02:41Z day: '01' department: - _id: EdHa doi: 10.1038/s41567-020-01037-7 ec_funded: 1 external_id: isi: - '000573519500002' intvolume: ' 17' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.05.15.096479 month: '02' oa: 1 oa_version: Preprint page: 267-274 project: - _id: 268294B6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P31639 name: Active mechano-chemical description of the cell cytoskeleton - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: Nature Physics publication_identifier: eissn: - '17452481' issn: - '17452473' publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/wound-healing-waves/ record: - id: '12964' relation: dissertation_contains status: public scopus_import: '1' status: public title: Theory of mechanochemical patterning and optimal migration in cell monolayers type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 17 year: '2021' ... --- _id: '9244' abstract: - lang: eng 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.' 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.)." article_number: e60916 article_processing_charge: No article_type: original author: - first_name: Simona full_name: Hankeova, Simona last_name: Hankeova - first_name: Jakub full_name: Salplachta, Jakub last_name: Salplachta - first_name: Tomas full_name: Zikmund, Tomas last_name: Zikmund - first_name: Michaela full_name: Kavkova, Michaela last_name: Kavkova - first_name: Noémi full_name: Van Hul, Noémi last_name: Van Hul - first_name: Adam full_name: Brinek, Adam last_name: Brinek - first_name: Veronika full_name: Smekalova, Veronika last_name: Smekalova - first_name: Jakub full_name: Laznovsky, Jakub last_name: Laznovsky - first_name: Feven full_name: Dawit, Feven last_name: Dawit - first_name: Josef full_name: Jaros, Josef last_name: Jaros - first_name: Vítězslav full_name: Bryja, Vítězslav last_name: Bryja - first_name: Urban full_name: Lendahl, Urban last_name: Lendahl - first_name: Ewa full_name: Ellis, Ewa last_name: Ellis - first_name: Antal full_name: Nemeth, Antal last_name: Nemeth - first_name: Björn full_name: Fischler, Björn last_name: Fischler - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Jozef full_name: Kaiser, Jozef last_name: Kaiser - first_name: Emma Rachel full_name: Andersson, Emma Rachel last_name: Andersson citation: 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. eLife. 2021;10. doi:10.7554/eLife.60916 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. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.60916 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.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/eLife.60916. ieee: S. Hankeova et al., “DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome,” eLife, vol. 10. eLife Sciences Publications, 2021. 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. mla: Hankeova, Simona, et al. “DUCT Reveals Architectural Mechanisms Contributing to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” ELife, vol. 10, e60916, eLife Sciences Publications, 2021, doi:10.7554/eLife.60916. 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). date_created: 2021-03-14T23:01:34Z date_published: 2021-02-26T00:00:00Z date_updated: 2023-08-07T14:12:54Z day: '26' ddc: - '570' department: - _id: EdHa doi: 10.7554/eLife.60916 ec_funded: 1 external_id: isi: - '000625357100001' pmid: - '33635272' file: - access_level: open_access checksum: 20ccf4dfe46c48cf986794c8bf4fd1cb content_type: application/pdf creator: dernst date_created: 2021-03-22T08:50:33Z date_updated: 2021-03-22T08:50:33Z file_id: '9271' file_name: 2021_eLife_Hankeova.pdf file_size: 9259690 relation: main_file success: 1 file_date_updated: 2021-03-22T08:50:33Z has_accepted_license: '1' intvolume: ' 10' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: eLife publication_identifier: eissn: - 2050084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 10 year: '2021' ...