--- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '21383' abstract: - lang: eng text: 'Planarian flatworms are known for their remarkable regenerative capacity; however, the precise intercellular communication mechanisms underlying this process remain unsolved. Here, we report the discovery and characterization of abundant extracellular vesicles (EVs) in planarians. Using imaging and molecular analysis, we show conservation of biogenesis, morphology, and protein composition of planarian EVs. Environmental stressors significantly elevate EV release, indicating that planarians dynamically regulate vesicle production. Functionally, planarian EVs mediate intercellular communication by transferring regulatory signals: We find that they shuttle small RNAs that effect systemic RNA interference (RNAi) throughout the organism. Notably, gene knockdown experiments reveal a crucial role for AGO-3, a member of the Argonaute family of proteins, in modulating the association of small interfering RNAs with EVs, linking the intracellular RNAi machinery to EV-based signaling. These findings highlight EVs as pivotal mediators of cell-cell communication in planarians, with broad implications for understanding the coordination of gene regulation and tissue regeneration in animals.' acknowledgement: 'We thank all the Sánchez Alvarado lab members for inputs and discussions. We are grateful to the Stowers Aquatics (particularly the Planarian team), Microscopy, and Molecular Biology core facilities for technical contributions and method development; e. n. lissek and A. Fujii from Oni US and S. Wang from the University of Missouri, Kansas city, for assistance with dStORM imaging; and d. Alburty and A. Page from innovaprep for assisting with the ntA. We also thank M. Miller for the illustrations. This work was supported by the hhMi and Stowers institute. ' article_number: eady1461 article_processing_charge: Yes article_type: original author: - first_name: Vidyanand full_name: Sasidharan, Vidyanand last_name: Sasidharan - first_name: Laura full_name: Ancellotti, Laura last_name: Ancellotti - first_name: Viraj full_name: Doddihal, Viraj id: 034e0824-174b-11ef-b32b-9366a0e70d1c last_name: Doddihal - first_name: Carolyn full_name: Brewster, Carolyn last_name: Brewster - first_name: Frederick full_name: Mann, Frederick last_name: Mann - first_name: Mary Cathleen full_name: McKinney, Mary Cathleen last_name: McKinney - first_name: Joseph full_name: Varberg, Joseph last_name: Varberg - first_name: Eric full_name: Ross, Eric last_name: Ross - first_name: Fengyan full_name: Deng, Fengyan last_name: Deng - first_name: Kexi full_name: Yi, Kexi last_name: Yi - first_name: Alejandro full_name: Sánchez Alvarado, Alejandro last_name: Sánchez Alvarado citation: ama: Sasidharan V, Ancellotti L, Doddihal V, et al. Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians. Science Advances. 2026;12(6). doi:10.1126/sciadv.ady1461 apa: Sasidharan, V., Ancellotti, L., Doddihal, V., Brewster, C., Mann, F., McKinney, M. C., … Sánchez Alvarado, A. (2026). Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.ady1461 chicago: Sasidharan, Vidyanand, Laura Ancellotti, Viraj Doddihal, Carolyn Brewster, Frederick Mann, Mary Cathleen McKinney, Joseph Varberg, et al. “Extracellular Vesicles Mediate Stem Cell Signaling and Systemic RNAi in Planarians.” Science Advances. American Association for the Advancement of Science, 2026. https://doi.org/10.1126/sciadv.ady1461. ieee: V. Sasidharan et al., “Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians,” Science Advances, vol. 12, no. 6. American Association for the Advancement of Science, 2026. ista: Sasidharan V, Ancellotti L, Doddihal V, Brewster C, Mann F, McKinney MC, Varberg J, Ross E, Deng F, Yi K, Sánchez Alvarado A. 2026. Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians. Science Advances. 12(6), eady1461. mla: Sasidharan, Vidyanand, et al. “Extracellular Vesicles Mediate Stem Cell Signaling and Systemic RNAi in Planarians.” Science Advances, vol. 12, no. 6, eady1461, American Association for the Advancement of Science, 2026, doi:10.1126/sciadv.ady1461. short: V. Sasidharan, L. Ancellotti, V. Doddihal, C. Brewster, F. Mann, M.C. McKinney, J. Varberg, E. Ross, F. Deng, K. Yi, A. Sánchez Alvarado, Science Advances 12 (2026). date_created: 2026-03-02T10:08:07Z date_published: 2026-02-01T00:00:00Z date_updated: 2026-03-02T14:23:22Z day: '01' ddc: - '570' department: - _id: CaHe doi: 10.1126/sciadv.ady1461 file: - access_level: open_access checksum: fa9f6dafe3538e2d2872c098e06d1712 content_type: application/pdf creator: dernst date_created: 2026-03-02T14:19:35Z date_updated: 2026-03-02T14:19:35Z file_id: '21389' file_name: 2026_ScienceAdv_Sasidharan.pdf file_size: 2841345 relation: main_file success: 1 file_date_updated: 2026-03-02T14:19:35Z has_accepted_license: '1' intvolume: ' 12' issue: '6' language: - iso: eng license: https://creativecommons.org/licenses/by-nc/4.0/ month: '02' oa: 1 oa_version: Published Version publication: Science Advances publication_identifier: eissn: - 2375-2548 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' scopus_import: '1' status: public title: Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 12 year: '2026' ... --- OA_place: repository OA_type: free access _id: '21137' acknowledged_ssus: - _id: Bio - _id: EM-Fac - _id: ScienComp - _id: LifeSc acknowledgement: We thank all members of the Heisenberg, Henkes, and Hannezo groups for their support. We are also grateful to the Imaging and Optics, Scientific Computing, Life Science Support, and Cryo-Electron Microscopy facilities at ISTA for their technical assistance and support. Numerical simulations were performed using the computational resources from Lorentz Institute and the Academic Leiden Interdisciplinary Cluster Environment (ALICE) provided by Leiden University, and from PMMH provided by Sorbonne Université. S.N has received funding from European Union’s Horizon 2020 research and innovation programme (grant agreement No. 665385). This work was supported by the Austrian Science Fund (FWF) under projects PAT5044023 and W1250 awarded to C.-P.H. article_processing_charge: No author: - first_name: Suyash full_name: Naik, Suyash id: 2C0B105C-F248-11E8-B48F-1D18A9856A87 last_name: Naik orcid: 0000-0001-8421-5508 citation: ama: Naik S. Data associated with Keratins coordinate tissue spreading . 2026. doi:10.15479/AT-ISTA-21137 apa: Naik, S. (2026). Data associated with Keratins coordinate tissue spreading . Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-21137 chicago: Naik, Suyash. “Data Associated with Keratins Coordinate Tissue Spreading .” Institute of Science and Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-21137. ieee: S. Naik, “Data associated with Keratins coordinate tissue spreading .” Institute of Science and Technology Austria, 2026. ista: Naik S. 2026. Data associated with Keratins coordinate tissue spreading , Institute of Science and Technology Austria, 10.15479/AT-ISTA-21137. mla: Naik, Suyash. Data Associated with Keratins Coordinate Tissue Spreading . Institute of Science and Technology Austria, 2026, doi:10.15479/AT-ISTA-21137. short: S. Naik, (2026). contributor: - contributor_type: researcher first_name: Yann-Edwin last_name: Keta - contributor_type: supervisor first_name: 'Silke ' last_name: Henkes - contributor_type: supervisor first_name: Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 - contributor_type: supervisor first_name: Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 corr_author: '1' date_created: 2026-02-04T16:38:02Z date_published: 2026-03-24T00:00:00Z date_updated: 2026-03-24T08:32:00Z day: '24' department: - _id: GradSch - _id: CaHe - _id: EdHa doi: 10.15479/AT-ISTA-21137 ec_funded: 1 file: - access_level: open_access checksum: 5d1fda7e410f24c311fcf6bcf725698f content_type: application/zip creator: snaik date_created: 2026-03-16T11:51:10Z date_updated: 2026-03-16T11:51:10Z description: 'Python3 library written in C++20 to integrate vertex models. Please read the readme at https://github.com/yketa/cells/blob/main/README.md for detailed instructions for installation and usage of the code in this repository. ' file_id: '21461' file_name: cells-main.zip file_size: 725916 relation: main_file title: Cell git repository - access_level: open_access checksum: ee350c8eaed99f3ca348c47c8b190d3c content_type: application/x-zip-compressed creator: snaik date_created: 2026-03-18T14:52:02Z date_updated: 2026-03-18T14:52:02Z file_id: '21464' file_name: DevBranchDataRepo.zip file_size: 282168895 relation: main_file success: 1 - access_level: open_access checksum: 1ecaf2c1a2ce8ff9c75a128cc02d0b8f content_type: text/markdown creator: snaik date_created: 2026-03-18T15:01:32Z date_updated: 2026-03-18T15:01:32Z file_id: '21466' file_name: ReadMe.md file_size: 2231 relation: main_file success: 1 - access_level: open_access checksum: da9a4687e5144b61a64ca341f922046a content_type: image/svg+xml creator: snaik date_created: 2026-03-18T15:12:57Z date_updated: 2026-03-18T15:12:57Z file_id: '21467' file_name: PaperSchematics.svg file_size: 1951210 relation: main_file success: 1 - access_level: open_access checksum: 9ac1054b16c212c6f34d402dce2c80e0 content_type: application/octet-stream creator: snaik date_created: 2026-03-21T03:37:43Z date_updated: 2026-03-21T03:37:43Z file_id: '21468' file_name: maxwell_sketch.tex file_size: 1897 relation: main_file success: 1 - access_level: open_access checksum: 7c9ecf78e2593b3830d96fa94baa08df content_type: application/x-zip-compressed creator: snaik date_created: 2026-03-24T07:21:43Z date_updated: 2026-03-24T07:21:43Z file_id: '21495' file_name: DataRepo.zip file_size: 749368723 relation: main_file success: 1 file_date_updated: 2026-03-24T07:21:43Z has_accepted_license: '1' license: https://creativecommons.org/licenses/by-sa/4.0/ month: '3' oa: 1 oa_version: None project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 8f060199-16d5-11f0-9cad-f3253b266c46 grant_number: PAT 5044023 name: Keratins in epithelial tissue spreading - _id: 252C3B08-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1250-B20 name: Nano-Analytics of Cellular Systems publisher: Institute of Science and Technology Austria status: public title: 'Data associated with Keratins coordinate tissue spreading ' tmp: image: /images/cc_by_sa.png legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0) short: CC BY-SA (4.0) type: research_data user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d year: '2026' ... --- OA_place: publisher OA_type: hybrid PlanS_conform: '1' _id: '21015' abstract: - lang: eng text: Early embryo geometry is one of the most invariant species-specific traits, yet its role in ensuring developmental reproducibility and robustness remains underexplored. Here we show that in zebrafish, the geometry of the fertilized egg—specifically its curvature and volume—serves as a critical initial condition triggering a cascade of events that influence development. The embryo geometry guides patterned asymmetric cell divisions in the blastoderm, generating radial gradients of cell volume and nucleocytoplasmic ratio. These gradients generate mitotic phase waves, with the nucleocytoplasmic ratio determining individual cell cycle periods independently of other cells. We demonstrate that reducing cell autonomy reshapes these waves, emphasizing the instructive role of geometry-derived volume patterns in setting the intrinsic period of the cell cycle oscillator. In addition to organizing cell cycles, early embryo geometry spatially patterns zygotic genome activation at the midblastula transition, a key step in establishing embryonic autonomy. Disrupting the embryo shape alters the zygotic genome activation pattern and causes ectopic germ layer specification, underscoring the developmental significance of geometry. Together, our findings reveal a symmetry-breaking function of early embryo geometry in coordinating cell cycle and transcriptional patterning. acknowledged_ssus: - _id: PreCl - _id: Bio - _id: ScienComp - _id: LifeSc acknowledgement: We thank N. Petridou (EMBL) for sharing results before publication. N.M. was supported by funding from the European Union’s Horizon 2020 programme under the Marie Skłodowska-Curie COFUND Actions ISTplus grant agreement number 754411. Y.I.L. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 101034413. The research was supported by funding to C.-P.H. from the NOMIS Foundation, Project ID 1.844. We would like to thank past and present members of the Heisenberg and Hannezo groups for discussions, particularly S. Shamipour, V. Doddihal, M. Jovic, N. Hino, F. N. Arslan, R. Kobylinska and C. Camelo for feedback on the draft manuscript. This research was supported by the Scientific Service Units (SSU) of Institute of Science and Technology Austria through resources provided by the Aquatics Facility, Imaging & Optics Facility (IOF), Scientific Computing (SciComp) facility and Lab Support Facility (LSF). Open access funding provided by Institute of Science and Technology (IST Austria). article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Nikhil full_name: Mishra, Nikhil id: C4D70E82-1081-11EA-B3ED-9A4C3DDC885E last_name: Mishra orcid: 0000-0002-6425-5788 - first_name: Yuting I full_name: Li, Yuting I id: ee7a5ca8-8b71-11ed-b662-b3341c05b7eb last_name: Li - 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: Mishra N, Li YI, Hannezo EB, Heisenberg C-PJ. Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo. Nature Physics. 2026;22:139-150. doi:10.1038/s41567-025-03122-1 apa: Mishra, N., Li, Y. I., Hannezo, E. B., & Heisenberg, C.-P. J. (2026). Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-025-03122-1 chicago: Mishra, Nikhil, Yuting I Li, Edouard B Hannezo, and Carl-Philipp J Heisenberg. “Geometry-Driven Asymmetric Cell Divisions Pattern Cell Cycles and Zygotic Genome Activation in the Zebrafish Embryo.” Nature Physics. Springer Nature, 2026. https://doi.org/10.1038/s41567-025-03122-1. ieee: N. Mishra, Y. I. Li, E. B. Hannezo, and C.-P. J. Heisenberg, “Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo,” Nature Physics, vol. 22. Springer Nature, pp. 139–150, 2026. ista: Mishra N, Li YI, Hannezo EB, Heisenberg C-PJ. 2026. Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo. Nature Physics. 22, 139–150. mla: Mishra, Nikhil, et al. “Geometry-Driven Asymmetric Cell Divisions Pattern Cell Cycles and Zygotic Genome Activation in the Zebrafish Embryo.” Nature Physics, vol. 22, Springer Nature, 2026, pp. 139–50, doi:10.1038/s41567-025-03122-1. short: N. Mishra, Y.I. Li, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 22 (2026) 139–150. corr_author: '1' date_created: 2026-01-20T10:12:19Z date_published: 2026-01-05T00:00:00Z date_updated: 2026-04-28T12:55:30Z day: '05' ddc: - '570' department: - _id: EdHa - _id: CaHe doi: 10.1038/s41567-025-03122-1 ec_funded: 1 external_id: oaworkid: - W7118187193 file: - access_level: open_access checksum: 0ab7ac2fbcb61a364dba57152db64ed7 content_type: application/pdf creator: dernst date_created: 2026-01-21T08:21:11Z date_updated: 2026-01-21T08:21:11Z file_id: '21026' file_name: 2026_NaturePhysics_Mishra.pdf file_size: 7335694 relation: main_file success: 1 file_date_updated: 2026-01-21T08:21:11Z has_accepted_license: '1' intvolume: ' 22' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '01' oa: 1 oa_version: Published Version oaworkid: 1 page: 139-150 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c call_identifier: H2020 grant_number: '101034413' name: 'IST-BRIDGE: International postdoctoral program' - _id: 917c023a-16d5-11f0-9cad-eb5cafc52090 name: Cytoplasmic self-organization into cell-like compartments as a common guiding principle in early animal development publication: Nature Physics publication_identifier: eissn: - 1745-2481 issn: - 1745-2473 issnl: - ' 1745-2473' publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on ISTA website relation: research_data url: https://ista.ac.at/en/news/geometry-shapes-life/ scopus_import: '1' status: public title: Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo 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: ba8df636-2132-11f1-aed0-ed93e2281fdd volume: 22 year: '2026' ... --- OA_place: publisher OA_type: hybrid PlanS_conform: '1' _id: '20048' abstract: - lang: eng text: 'During embryonic development, cell behaviors need to be tightly regulated in time and space. Yet how the temporal and spatial regulations of cell behaviors are interconnected during embryonic development remains elusive. To address this, we turned to zebrafish gastrulation, the process whereby dynamic cell behaviors generate the three principal germ layers of the early embryo. Here, we show that Hoxb cluster genes are expressed in a temporally collinear manner at the blastoderm margin, where mesodermal and endodermal (mesendoderm) progenitor cells are specified and ingress to form mesendoderm/hypoblast. Functional analysis shows that these Hoxb genes regulate the timing of cell ingression: under- or overexpression of Hoxb genes perturb the timing of mesendoderm cell ingression and, consequently, the positioning of these cells along the forming anterior-posterior body axis after gastrulation. Finally, we found that Hoxb genes control the timing of mesendoderm ingression by regulating cellular bleb formation and cell surface fluctuations in the ingressing cells. Collectively, our findings suggest that Hoxb genes interconnect the temporal and spatial pattern of cell behaviors during zebrafish gastrulation by controlling cell surface fluctuations.' acknowledgement: We thank all the Heisenberg lab members for discussions and comments on the manuscript, and the Bioimaging and Life Science facilities of ISTA for support with microscopy and fish maintenance, respectively. This study was funded by a Japan Society for the Promotion of Science (JSPS) Overseas Research Fellowship and a Japan Science and Technology Agency PRESTO grant (JPMJPR214B) to Y.M. Open Access funding provided by the Japan Science and Technology Agency. Deposited in PMC for immediate release. article_number: dev204261 article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Yuuta full_name: Moriyama, Yuuta id: addc9b8c-67a0-11f0-b374-a2e094825470 last_name: Moriyama orcid: 0000-0002-2853-8051 - first_name: Toshiyuki full_name: Mitsui, Toshiyuki last_name: Mitsui - 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: Moriyama Y, Mitsui T, Heisenberg C-PJ. Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation. Development. 2025;152(12). doi:10.1242/dev.204261 apa: Moriyama, Y., Mitsui, T., & Heisenberg, C.-P. J. (2025). Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation. Development. The Company of Biologists. https://doi.org/10.1242/dev.204261 chicago: Moriyama, Yuuta, Toshiyuki Mitsui, and Carl-Philipp J Heisenberg. “Hoxb Genes Determine the Timing of Cell Ingression by Regulating Cell Surface Fluctuations during Zebrafish Gastrulation.” Development. The Company of Biologists, 2025. https://doi.org/10.1242/dev.204261. ieee: Y. Moriyama, T. Mitsui, and C.-P. J. Heisenberg, “Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation,” Development, vol. 152, no. 12. The Company of Biologists, 2025. ista: Moriyama Y, Mitsui T, Heisenberg C-PJ. 2025. Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation. Development. 152(12), dev204261. mla: Moriyama, Yuuta, et al. “Hoxb Genes Determine the Timing of Cell Ingression by Regulating Cell Surface Fluctuations during Zebrafish Gastrulation.” Development, vol. 152, no. 12, dev204261, The Company of Biologists, 2025, doi:10.1242/dev.204261. short: Y. Moriyama, T. Mitsui, C.-P.J. Heisenberg, Development 152 (2025). corr_author: '1' date_created: 2025-07-21T08:10:32Z date_published: 2025-06-27T00:00:00Z date_updated: 2025-09-30T14:07:51Z day: '27' ddc: - '570' department: - _id: CaHe doi: 10.1242/dev.204261 external_id: isi: - '001525252300001' pmid: - '40576478' file: - access_level: open_access checksum: 808d8aa28df79d23fb661838d1fdc1be content_type: application/pdf creator: dernst date_created: 2025-07-23T08:43:01Z date_updated: 2025-07-23T08:43:01Z file_id: '20070' file_name: 2025_Development_Moriyama.pdf file_size: 25935563 relation: main_file success: 1 file_date_updated: 2025-07-23T08:43:01Z has_accepted_license: '1' intvolume: ' 152' isi: 1 issue: '12' language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 publication: Development publication_identifier: eissn: - 1477-9129 issn: - 0950-1991 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 152 year: '2025' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold PlanS_conform: '1' _id: '20183' abstract: - lang: eng text: The unequal segregation of organelles has been proposed to be an intrinsic mechanism that contributes to cell fate divergence during asymmetric cell division; however, in vivo evidence is sparse. Using super-resolution microscopy, we analysed the segregation of organelles during the division of the neuroblast QL.p in C. elegans larvae. QL.p divides to generate a daughter that survives, QL.pa, and a daughter that dies, QL.pp. We found that mitochondria segregate unequally by density and morphology and that this is dependent on mitochondrial dynamics. Furthermore, we found that mitochondrial density in QL.pp correlates with the time it takes QL.pp to die. We propose that low mitochondrial density in QL.pp promotes the cell death fate and ensures that QL.pp dies in a highly reproducible and timely manner. Our results provide in vivo evidence that the unequal segregation of mitochondria can contribute to cell fate divergence during asymmetric cell division in a developing animal. acknowledgement: We thank members of the Conradt lab, the Center for Cell and Molecular Dynamics (https://www.uclccmd.co.uk/) and T. Schedl for discussions and comments on the manuscript. We thank L. McGuinness for excellent technical support. Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We thank Alex Hajnal (University of Zurich, Switzerland) and Andrew deMello (ETH Zurich, Switzerland) for their support of S.B. This work was supported by a predoctoral fellowship from the Studienstiftung des deutschen Volkes to NM, funds from UCL (Division of Biosciences, UCL LSM Capital Equipment Fund) to B.C., and a Wolfson Fellowship from the Royal Society (https://royalsociety.org/) to B.C. (RSWF\R1\180008), and the Biotechnology and Biological Sciences Research Council (https://bbsrc.ukri.org/) (BB/V007572/1 and BB/V015648/1to B.C.). article_number: '7174' article_processing_charge: Yes article_type: original author: - first_name: Ioannis full_name: Segos, Ioannis last_name: Segos - first_name: Jens full_name: Van Eeckhoven, Jens last_name: Van Eeckhoven - first_name: Simon full_name: Berger, Simon last_name: Berger - first_name: Nikhil full_name: Mishra, Nikhil id: C4D70E82-1081-11EA-B3ED-9A4C3DDC885E last_name: Mishra orcid: 0000-0002-6425-5788 - first_name: Eric J. full_name: Lambie, Eric J. last_name: Lambie - first_name: Barbara full_name: Conradt, Barbara last_name: Conradt citation: ama: Segos I, Van Eeckhoven J, Berger S, Mishra N, Lambie EJ, Conradt B. Unequal segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in sister cells in vivo. Nature Communications. 2025;16. doi:10.1038/s41467-025-62484-5 apa: Segos, I., Van Eeckhoven, J., Berger, S., Mishra, N., Lambie, E. J., & Conradt, B. (2025). Unequal segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in sister cells in vivo. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-025-62484-5 chicago: Segos, Ioannis, Jens Van Eeckhoven, Simon Berger, Nikhil Mishra, Eric J. Lambie, and Barbara Conradt. “Unequal Segregation of Mitochondria during Asymmetric Cell Division Contributes to Cell Fate Divergence in Sister Cells in Vivo.” Nature Communications. Springer Nature, 2025. https://doi.org/10.1038/s41467-025-62484-5. ieee: I. Segos, J. Van Eeckhoven, S. Berger, N. Mishra, E. J. Lambie, and B. Conradt, “Unequal segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in sister cells in vivo,” Nature Communications, vol. 16. Springer Nature, 2025. ista: Segos I, Van Eeckhoven J, Berger S, Mishra N, Lambie EJ, Conradt B. 2025. Unequal segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in sister cells in vivo. Nature Communications. 16, 7174. mla: Segos, Ioannis, et al. “Unequal Segregation of Mitochondria during Asymmetric Cell Division Contributes to Cell Fate Divergence in Sister Cells in Vivo.” Nature Communications, vol. 16, 7174, Springer Nature, 2025, doi:10.1038/s41467-025-62484-5. short: I. Segos, J. Van Eeckhoven, S. Berger, N. Mishra, E.J. Lambie, B. Conradt, Nature Communications 16 (2025). date_created: 2025-08-17T22:01:35Z date_published: 2025-08-04T00:00:00Z date_updated: 2025-09-01T09:47:29Z day: '04' ddc: - '570' department: - _id: CaHe doi: 10.1038/s41467-025-62484-5 external_id: pmid: - '40759648' file: - access_level: open_access checksum: f28e73963ea1f55876d0d1afca0f706a content_type: application/pdf creator: dernst date_created: 2025-09-01T09:46:44Z date_updated: 2025-09-01T09:46:44Z file_id: '20261' file_name: 2025_NatureComm_Segos.pdf file_size: 3775190 relation: main_file success: 1 file_date_updated: 2025-09-01T09:46:44Z has_accepted_license: '1' intvolume: ' 16' language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Unequal segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in sister cells in vivo 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 16 year: '2025' ... --- OA_place: publisher OA_type: hybrid PlanS_conform: '1' _id: '20188' abstract: - lang: eng text: Collective cell migration is coordinated by the front-to-rear intercellular propagation of EGFR-Ras-ERK pathway activation. However, the molecular mechanisms integrating front-to-rear information into this intercellular signaling cascade, particularly the determinants of cellular front-side specification, remain elusive. We visualized the activity of EGFR, Ras, Rac1 and Rab5A (hereafter Rab5) by using FRET biosensors and chemogenetic tools. Whereas EGFR activation was uniformly observed within cells, Ras activation was biased to the front side within cells. The polarized Ras activation depended on Merlin and Rac1, which also showed front-biased activation. Furthermore, Rab5, a crucial regulator of cell migration, demonstrated similar front-biased activation and was found to function downstream of Ras while being necessary for Rac1 activation. Thus, the positive feedback loop consisting of Ras, Rab5 and Rac1 is activated primarily at the front of collectively migrating cells. These findings offer new spatio-temporal insight into processing front–rear information during collective cell migration. acknowledgement: We are grateful to the members of the Matsuda Laboratory for their helpful input, to K. Hirano, T. Uesugi and K. Takakura, who provided technical assistance, and to the Medical Research Support Center of Kyoto University for DNA sequence analysis. This work was supported by the Kyoto University Live Imaging Center. Financial support was provided by Japan Society for the Promotion of Science (JSPS) KAKENHI grants (21H05226 to K.T., 19H00993 and 20H05898 to M.M.), a Japan Science and Technology Agency (JST) CREST grant (JPMJCR1654 to M.M.), and a JST Moonshot Research and Development Program grant (JPMJPS2022 to M.M.). Open Access funding provided by Tokushima University. Deposited in PMC for immediate release. article_number: '263779' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Yuya full_name: Jikko, Yuya last_name: Jikko - first_name: Eriko full_name: Deguchi, Eriko last_name: Deguchi - first_name: Kimiya full_name: Matsuda, Kimiya last_name: Matsuda - first_name: Naoya full_name: Hino, Naoya id: 5299a9ce-7679-11eb-a7bc-d1e62b936307 last_name: Hino - first_name: Shinya full_name: Tsukiji, Shinya last_name: Tsukiji - first_name: Michiyuki full_name: Matsuda, Michiyuki last_name: Matsuda - first_name: Kenta full_name: Terai, Kenta last_name: Terai citation: ama: Jikko Y, Deguchi E, Matsuda K, et al. Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration. Journal of Cell Science. 2025;138(15). doi:10.1242/jcs.263779 apa: Jikko, Y., Deguchi, E., Matsuda, K., Hino, N., Tsukiji, S., Matsuda, M., & Terai, K. (2025). Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.263779 chicago: Jikko, Yuya, Eriko Deguchi, Kimiya Matsuda, Naoya Hino, Shinya Tsukiji, Michiyuki Matsuda, and Kenta Terai. “Front-Biased Activation of the Ras-Rab5-Rac1 Loop Coordinates Collective Cell Migration.” Journal of Cell Science. The Company of Biologists, 2025. https://doi.org/10.1242/jcs.263779. ieee: Y. Jikko et al., “Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration,” Journal of Cell Science, vol. 138, no. 15. The Company of Biologists, 2025. ista: Jikko Y, Deguchi E, Matsuda K, Hino N, Tsukiji S, Matsuda M, Terai K. 2025. Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration. Journal of Cell Science. 138(15), 263779. mla: Jikko, Yuya, et al. “Front-Biased Activation of the Ras-Rab5-Rac1 Loop Coordinates Collective Cell Migration.” Journal of Cell Science, vol. 138, no. 15, 263779, The Company of Biologists, 2025, doi:10.1242/jcs.263779. short: Y. Jikko, E. Deguchi, K. Matsuda, N. Hino, S. Tsukiji, M. Matsuda, K. Terai, Journal of Cell Science 138 (2025). date_created: 2025-08-17T22:01:36Z date_published: 2025-08-01T00:00:00Z date_updated: 2025-11-27T14:12:24Z day: '01' ddc: - '570' department: - _id: CaHe doi: 10.1242/jcs.263779 external_id: isi: - '001567723900009' pmid: - '40667649' file: - access_level: open_access checksum: 29f42619dab5ce251a20c769ed4581c0 content_type: application/pdf creator: dernst date_created: 2025-09-01T10:02:24Z date_updated: 2025-09-01T10:02:24Z file_id: '20262' file_name: 2025_JourCellScience_Jikko.pdf file_size: 12393297 relation: main_file success: 1 file_date_updated: 2025-09-01T10:02:24Z has_accepted_license: '1' intvolume: ' 138' isi: 1 issue: '15' language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - ' 0021-9533' publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 138 year: '2025' ... --- OA_place: publisher OA_type: hybrid PlanS_conform: '1' _id: '20349' abstract: - lang: eng text: Oogenesis – the formation and development of an oocyte – is fundamental to reproduction and embryonic development. Due to its accessibility to genetic manipulations and the ability to culture and experimentally manipulate oocytes ex vivo, zebrafish has emerged as a powerful vertebrate model system for studying oogenesis. In this review, we provide a comprehensive overview of zebrafish oogenesis, from early germ cell formation to oocyte maturation and fertilization. We discuss recent advances in uncovering the molecular and cellular mechanisms driving this complex process and highlight key knowledge gaps that remain to be addressed. acknowledgement: We thank Carolina Camelo for making schematics for this review. article_number: '103650' article_processing_charge: Yes (via OA deal) article_type: review author: - first_name: Laura full_name: Hofmann, Laura id: b88d43f2-dc74-11ea-a0a7-e41b7912e031 last_name: Hofmann - 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: 'Hofmann L, Heisenberg C-PJ. Decoding zebrafish oogenesis: From primordial germ cell development to fertilization. Seminars in Cell and Developmental Biology. 2025;175. doi:10.1016/j.semcdb.2025.103650' apa: 'Hofmann, L., & Heisenberg, C.-P. J. (2025). Decoding zebrafish oogenesis: From primordial germ cell development to fertilization. Seminars in Cell and Developmental Biology. Elsevier. https://doi.org/10.1016/j.semcdb.2025.103650' chicago: 'Hofmann, Laura, and Carl-Philipp J Heisenberg. “Decoding Zebrafish Oogenesis: From Primordial Germ Cell Development to Fertilization.” Seminars in Cell and Developmental Biology. Elsevier, 2025. https://doi.org/10.1016/j.semcdb.2025.103650.' ieee: 'L. Hofmann and C.-P. J. Heisenberg, “Decoding zebrafish oogenesis: From primordial germ cell development to fertilization,” Seminars in Cell and Developmental Biology, vol. 175. Elsevier, 2025.' ista: 'Hofmann L, Heisenberg C-PJ. 2025. Decoding zebrafish oogenesis: From primordial germ cell development to fertilization. Seminars in Cell and Developmental Biology. 175, 103650.' mla: 'Hofmann, Laura, and Carl-Philipp J. Heisenberg. “Decoding Zebrafish Oogenesis: From Primordial Germ Cell Development to Fertilization.” Seminars in Cell and Developmental Biology, vol. 175, 103650, Elsevier, 2025, doi:10.1016/j.semcdb.2025.103650.' short: L. Hofmann, C.-P.J. Heisenberg, Seminars in Cell and Developmental Biology 175 (2025). corr_author: '1' date_created: 2025-09-14T22:01:32Z date_published: 2025-12-01T00:00:00Z date_updated: 2025-12-30T10:21:13Z day: '01' ddc: - '570' department: - _id: CaHe doi: 10.1016/j.semcdb.2025.103650 external_id: isi: - '001567260100001' pmid: - '40913907' file: - access_level: open_access checksum: 80ea6cbb004853bb1e87db3422a74aca content_type: application/pdf creator: dernst date_created: 2025-12-30T10:21:00Z date_updated: 2025-12-30T10:21:00Z file_id: '20914' file_name: 2025_SemCellDevBiology_Hofmann.pdf file_size: 2778561 relation: main_file success: 1 file_date_updated: 2025-12-30T10:21:00Z has_accepted_license: '1' intvolume: ' 175' isi: 1 language: - iso: eng month: '12' oa: 1 oa_version: Published Version pmid: 1 publication: Seminars in Cell and Developmental Biology publication_identifier: eissn: - 1096-3634 issn: - 1084-9521 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'Decoding zebrafish oogenesis: From primordial germ cell development to fertilization' 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 175 year: '2025' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '19404' abstract: - lang: eng text: Cell migration is a fundamental process during embryonic development. Most studies in vivo have focused on the migration of cells using the extracellular matrix (ECM) as their substrate for migration. In contrast, much less is known about how cells migrate on other cells, as found in early embryos when the ECM has not yet formed. Here, we show that lateral mesendoderm (LME) cells in the early zebrafish gastrula use the ectoderm as their substrate for migration. We show that the lateral ectoderm is permissive for the animal-pole-directed migration of LME cells, while the ectoderm at the animal pole halts it. These differences in permissiveness depend on the lateral ectoderm being more cohesive than the animal ectoderm, a property controlled by bone morphogenetic protein (BMP) signaling within the ectoderm. Collectively, these findings identify ectoderm tissue cohesion as one critical factor in regulating LME migration during zebrafish gastrulation. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: ScienComp acknowledgement: 'We are grateful to the colleagues who contributed to this work with discussions, technical advice, and feedback on the manuscript: Irene Steccari, David Labrousse Arias and the other members of the Heisenberg lab, Nicole Amberg, Florian Pauler, Nicoletta Petridou, Elena Scarpa, and Edouard Hannezo. We also thank the Imaging and Optics Facility, the Life Science Facility, and the Scientific Computing Unit at ISTA for support. The Next Generation Sequencing Facility at Vienna BioCenter Core Facilities performed the RNA-seq for animal and lateral ectoderm. D.B.B. was supported by the NOMIS Foundation as a NOMIS Fellow and by an EMBO Postdoctoral Fellowship (ALTF 343-2022). S. Tavano was supported by an EMBO Postdoctoral Fellowship (ALTF 1159-2018).' article_number: '115387' article_processing_charge: Yes article_type: original author: - first_name: Ste full_name: Tavano, Ste id: 2F162F0C-F248-11E8-B48F-1D18A9856A87 last_name: Tavano orcid: 0000-0001-9970-7804 - first_name: David full_name: Brückner, David id: e1e86031-6537-11eb-953a-f7ab92be508d last_name: Brückner orcid: 0000-0001-7205-2975 - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Xin full_name: Tong, Xin id: 50F65CDC-AA30-11E9-A72B-8A12E6697425 last_name: Tong - first_name: Roland full_name: Kardos, Roland id: 4039350E-F248-11E8-B48F-1D18A9856A87 last_name: Kardos - first_name: Alexandra full_name: Schauer, Alexandra id: 30A536BA-F248-11E8-B48F-1D18A9856A87 last_name: Schauer orcid: 0000-0001-7659-9142 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - 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: Tavano S, Brückner D, Tasciyan S, et al. BMP-dependent patterning of ectoderm tissue material properties modulates lateral mesendoderm cell migration during early zebrafish gastrulation. Cell Reports. 2025;44(3). doi:10.1016/j.celrep.2025.115387 apa: Tavano, S., Brückner, D., Tasciyan, S., Tong, X., Kardos, R., Schauer, A., … Heisenberg, C.-P. J. (2025). BMP-dependent patterning of ectoderm tissue material properties modulates lateral mesendoderm cell migration during early zebrafish gastrulation. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2025.115387 chicago: Tavano, Ste, David Brückner, Saren Tasciyan, Xin Tong, Roland Kardos, Alexandra Schauer, Robert Hauschild, and Carl-Philipp J Heisenberg. “BMP-Dependent Patterning of Ectoderm Tissue Material Properties Modulates Lateral Mesendoderm Cell Migration during Early Zebrafish Gastrulation.” Cell Reports. Elsevier, 2025. https://doi.org/10.1016/j.celrep.2025.115387. ieee: S. Tavano et al., “BMP-dependent patterning of ectoderm tissue material properties modulates lateral mesendoderm cell migration during early zebrafish gastrulation,” Cell Reports, vol. 44, no. 3. Elsevier, 2025. ista: Tavano S, Brückner D, Tasciyan S, Tong X, Kardos R, Schauer A, Hauschild R, Heisenberg C-PJ. 2025. BMP-dependent patterning of ectoderm tissue material properties modulates lateral mesendoderm cell migration during early zebrafish gastrulation. Cell Reports. 44(3), 115387. mla: Tavano, Ste, et al. “BMP-Dependent Patterning of Ectoderm Tissue Material Properties Modulates Lateral Mesendoderm Cell Migration during Early Zebrafish Gastrulation.” Cell Reports, vol. 44, no. 3, 115387, Elsevier, 2025, doi:10.1016/j.celrep.2025.115387. short: S. Tavano, D. Brückner, S. Tasciyan, X. Tong, R. Kardos, A. Schauer, R. Hauschild, C.-P.J. Heisenberg, Cell Reports 44 (2025). corr_author: '1' date_created: 2025-03-16T23:01:24Z date_published: 2025-03-25T00:00:00Z date_updated: 2025-10-22T07:00:04Z day: '25' ddc: - '570' department: - _id: CaHe - _id: EdHa - _id: MiSi - _id: Bio doi: 10.1016/j.celrep.2025.115387 external_id: isi: - '001443652700001' pmid: - '40057955' file: - access_level: open_access checksum: 57e05dd1598c807af0afdb32cec039d3 content_type: application/pdf creator: dernst date_created: 2025-03-17T10:26:54Z date_updated: 2025-03-17T10:26:54Z file_id: '19413' file_name: 2025_CellReports_Tavano.pdf file_size: 9067797 relation: main_file success: 1 file_date_updated: 2025-03-17T10:26:54Z has_accepted_license: '1' intvolume: ' 44' isi: 1 issue: '3' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '03' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 34e2a5b5-11ca-11ed-8bc3-b2265616ef0b grant_number: ALTF 343-2022 name: A mechano-chemical theory for stem cell fate decisions in organoid development - _id: 269CD5C4-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1159-2018 name: 'Mechanosensation in cell migration: the role of friction forces in cell polarization and directed migration' publication: Cell Reports publication_identifier: eissn: - 2211-1247 issn: - 2639-1856 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: BMP-dependent patterning of ectoderm tissue material properties modulates lateral mesendoderm cell migration during early zebrafish gastrulation tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 44 year: '2025' ... --- OA_place: publisher _id: '20441' abstract: - lang: eng text: "Epithelial spreading plays a pivotal role in the development of organisms especially those\r\nsuch as zebrafish which require the epithelial enveloping layer (EVL) to spread to cover the\r\nsubstantial yolk surface during gastrulation. Epiboly requires the transition of the epithelium\r\nwith cuboidal cells to form a thin, flat squamous epithelial sheet. During this transition, the\r\ncells show tissue-scale mechanosensation with mechanisms such as direct mechanical control\r\nover the axis of cell division.\r\nCytoskeletal intermediate filaments play a crucial role in vertebrate cells, not only facilitating\r\nmechanical stability but also helping facilitate the mechanosensitive response of the cell.\r\nMechanosenstivity displayed by intermediate filaments is due not just to their interesting\r\nphysical properties but also to their interactions with other cytoskeletal elements such as actin\r\nand microtubules. Keratin is the predominant intermediate filament expressed in the EVL.\r\nIt expresses concomitantly with the gastrulation movements of the developing embryo. Our\r\nwork focuses on understanding the role and dynamics of the keratin cytoskeletal network in\r\nmodulating the physical aspects of EVL spreading. We demonstrated with the combination of\r\nphysical characterisation and manipulations of the EVL, utilising a variety of biophysical tools\r\nand microscopy, the mechanistic role of keratin in tissue spreading.\r\nGenerating novel genetic morphants and mutants, we probe the effect that the loss of the\r\nkeratin network has on the physiology of the epithelium and the developing embryo. We\r\nshow that the changing organisation of the keratin network is important for changing EVL\r\nphysical properties as the stress imposed on the EVL increases during epiboly. By modelling\r\nthe epithelium, we study how the mechanical heterogeneity in an epithelium can feed back into\r\na mechanical loop to the maturation of the keratin network and hence affect the mechanics\r\nof the epithelium. However, unlike what would be predicted by the effect of intermediate\r\nfilaments in acting as a security belt and increasing the resistance of the epithelium, we observe\r\nthat loss of keratin leads to a delay in the EVL movement. Using both local aspirations of the\r\nYSL and EVL ablations, we demonstrate the mechanistic facilitation of actin mechanosensation\r\nin a keratin-dependent manner.\r\nFurthermore, using chemical inhibitors of microtubule polymerisation, we provide insight into\r\nthe mechanisms underlying the organisation and distribution of keratin. Interestingly, the\r\nphenotype observed upon this loss of microtubules shows that keratins interact with the nucleus\r\nthrough microtubular interactions. Together with these diverse observations, we describe\r\nthe mechanosensory feedback between resilience and that is critical for uniform and robust\r\nspreading of the epithelium." acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: "I would also like to thank the LSF and Cryo facility at ISTA, which have been helpful in my\r\nexperiments. I would also like to acknowledge FWF, grant DOI 10.55776/PAT5044023 and JKU Nanocell grant DOI \r\n10.55776/W1250 for providing funding for my PhD research. EMBO and FWF for providing funding for travel grants to attend conferences." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Suyash full_name: Naik, Suyash id: 2C0B105C-F248-11E8-B48F-1D18A9856A87 last_name: Naik orcid: 0000-0001-8421-5508 citation: ama: Naik S. Keratins act as global coordinators of tissue spreading through mechanosensitive feedback. 2025. doi:10.15479/AT-ISTA-20441 apa: Naik, S. (2025). Keratins act as global coordinators of tissue spreading through mechanosensitive feedback. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20441 chicago: Naik, Suyash. “Keratins Act as Global Coordinators of Tissue Spreading through Mechanosensitive Feedback.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20441. ieee: S. Naik, “Keratins act as global coordinators of tissue spreading through mechanosensitive feedback,” Institute of Science and Technology Austria, 2025. ista: Naik S. 2025. Keratins act as global coordinators of tissue spreading through mechanosensitive feedback. Institute of Science and Technology Austria. mla: Naik, Suyash. Keratins Act as Global Coordinators of Tissue Spreading through Mechanosensitive Feedback. Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20441. short: S. Naik, Keratins Act as Global Coordinators of Tissue Spreading through Mechanosensitive Feedback, Institute of Science and Technology Austria, 2025. corr_author: '1' date_created: 2025-10-10T14:58:30Z date_published: 2025-10-12T00:00:00Z date_updated: 2026-04-07T11:58:57Z day: '12' ddc: - '596' - '597' - '532' degree_awarded: PhD department: - _id: GradSch - _id: CaHe - _id: EdHa doi: 10.15479/AT-ISTA-20441 file: - access_level: open_access checksum: 2892f04d4a5c18677871c3e06ac1244a content_type: application/pdf creator: snaik date_created: 2025-10-28T13:10:08Z date_updated: 2025-10-28T13:10:08Z file_id: '20567' file_name: Thesis_PDFA_.pdf file_size: 6846189 relation: main_file success: 1 - access_level: open_access checksum: 15934d4465cd0e9b7c32678da9a33a2f content_type: application/zip creator: snaik date_created: 2025-10-28T13:10:26Z date_updated: 2025-10-28T13:10:26Z file_id: '20568' file_name: Thesis.zip file_size: 8839300 relation: source_file file_date_updated: 2025-10-28T13:10:26Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '105' project: - _id: 8f060199-16d5-11f0-9cad-f3253b266c46 grant_number: PAT 5044023 name: Keratins in epithelial tissue spreading - _id: 25AA5F24-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W 1250-B20 name: Nano-Analytics of Cellular Systems publication_identifier: isbn: - 978-3-99078-069-5 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '20465' relation: part_of_dissertation status: public status: public supervisor: - 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 - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 title: Keratins act as global coordinators of tissue spreading through mechanosensitive feedback tmp: image: /images/cc_by_sa.png legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0) short: CC BY-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2025' ... --- OA_place: repository _id: '20465' abstract: - lang: eng text: For tissues to spread, they must be deformable while maintaining their structural integrity. How these opposing requirements are balanced within spreading tissues is not yet well understood. Here, we show that keratin intermediate filaments function in epithelial spreading by adapting tissue mechanical resilience to the stresses arising in the tissue during the spreading process. By analysing the expansion of the enveloping cell layer (EVL) over the large yolk cell in early zebrafish embryos in vivo, we found that keratin network maturation in EVL cells is promoted by stresses building up within the spreading tissue. Through genetic interference and tissue rheology experiments, complemented by a vertex model with mechanochemical feedback, we demonstrate that stress-induced keratin network maturation in the EVL increases tissue viscosity, which is essential for preventing tissue rupture. Interestingly, keratins are also required in the yolk cell for mechanosensitive actomyosin network contraction and flow, the force-generating processes pulling the EVL. These dual mechanosensitive functions of keratins enable a balance between pulling force production in the yolk cell and the mechanical resilience of the EVL against stresses generated by these pulling forces, thereby ensuring uniform and robust tissue spreading. article_processing_charge: No author: - first_name: Suyash full_name: Naik, Suyash id: 2C0B105C-F248-11E8-B48F-1D18A9856A87 last_name: Naik orcid: 0000-0001-8421-5508 - first_name: Yann-Edwin full_name: Keta, Yann-Edwin last_name: Keta - first_name: Kornelija full_name: Pranjic-Ferscha, Kornelija id: 4362B3C2-F248-11E8-B48F-1D18A9856A87 last_name: Pranjic-Ferscha - 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: Silke full_name: Henkes, Silke last_name: Henkes - 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: Naik S, Keta Y-E, Pranjic-Ferscha K, Hannezo EB, Henkes S, Heisenberg C-PJ. Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties. bioRxiv. doi:10.1101/2025.02.14.638262 apa: Naik, S., Keta, Y.-E., Pranjic-Ferscha, K., Hannezo, E. B., Henkes, S., & Heisenberg, C.-P. J. (n.d.). Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2025.02.14.638262 chicago: Naik, Suyash, Yann-Edwin Keta, Kornelija Pranjic-Ferscha, Edouard B Hannezo, Silke Henkes, and Carl-Philipp J Heisenberg. “Keratins Coordinate Tissue Spreading by Balancing Spreading Forces with Tissue Material Properties.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2025.02.14.638262. ieee: S. Naik, Y.-E. Keta, K. Pranjic-Ferscha, E. B. Hannezo, S. Henkes, and C.-P. J. Heisenberg, “Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties,” bioRxiv. Cold Spring Harbor Laboratory. ista: Naik S, Keta Y-E, Pranjic-Ferscha K, Hannezo EB, Henkes S, Heisenberg C-PJ. Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties. bioRxiv, 10.1101/2025.02.14.638262. mla: Naik, Suyash, et al. “Keratins Coordinate Tissue Spreading by Balancing Spreading Forces with Tissue Material Properties.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2025.02.14.638262. short: S. Naik, Y.-E. Keta, K. Pranjic-Ferscha, E.B. Hannezo, S. Henkes, C.-P.J. Heisenberg, BioRxiv (n.d.). corr_author: '1' date_created: 2025-10-14T07:25:27Z date_published: 2025-02-17T00:00:00Z date_updated: 2026-04-07T11:58:57Z day: '17' department: - _id: CaHe - _id: EdHa doi: 10.1101/2025.02.14.638262 language: - iso: eng license: https://creativecommons.org/licenses/by-nd/4.0/ main_file_link: - open_access: '1' url: https://doi.org/10.1101/2025.02.14.638262 month: '02' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: draft publisher: Cold Spring Harbor Laboratory related_material: record: - id: '20441' relation: dissertation_contains status: public status: public title: Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties tmp: image: /image/cc_by_nd.png legal_code_url: https://creativecommons.org/licenses/by-nd/4.0/legalcode name: Creative Commons Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0) short: CC BY-ND (4.0) type: preprint user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2025' ... --- OA_type: closed access _id: '18651' abstract: - lang: eng text: Embryo axis formation begins with the localized expression of biochemical signals, which organize cell movements and determine cell fate. A quail study finds that tissue contraction and resulting long-range changes in tissue tension restrict the area where these biochemical signals are expressed. article_processing_charge: No article_type: letter_note author: - first_name: Naoya full_name: Hino, Naoya id: 5299a9ce-7679-11eb-a7bc-d1e62b936307 last_name: Hino - first_name: Carolina full_name: Santos Fernandes Lasbarrères Camelo, Carolina id: 6347dca5-074c-11ed-af92-a80f860d9d5b last_name: Santos Fernandes Lasbarrères Camelo - 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: 'Hino N, Santos Fernandes Lasbarrères Camelo C, Heisenberg C-PJ. Development: Turing mechanics. Current Biology. 2024;34(24):R1230-R1232. doi:10.1016/j.cub.2024.10.065' apa: 'Hino, N., Santos Fernandes Lasbarrères Camelo, C., & Heisenberg, C.-P. J. (2024). Development: Turing mechanics. Current Biology. Elsevier. https://doi.org/10.1016/j.cub.2024.10.065' chicago: 'Hino, Naoya, Carolina Santos Fernandes Lasbarrères Camelo, and Carl-Philipp J Heisenberg. “Development: Turing Mechanics.” Current Biology. Elsevier, 2024. https://doi.org/10.1016/j.cub.2024.10.065.' ieee: 'N. Hino, C. Santos Fernandes Lasbarrères Camelo, and C.-P. J. Heisenberg, “Development: Turing mechanics,” Current Biology, vol. 34, no. 24. Elsevier, pp. R1230–R1232, 2024.' ista: 'Hino N, Santos Fernandes Lasbarrères Camelo C, Heisenberg C-PJ. 2024. Development: Turing mechanics. Current Biology. 34(24), R1230–R1232.' mla: 'Hino, Naoya, et al. “Development: Turing Mechanics.” Current Biology, vol. 34, no. 24, Elsevier, 2024, pp. R1230–32, doi:10.1016/j.cub.2024.10.065.' short: N. Hino, C. Santos Fernandes Lasbarrères Camelo, C.-P.J. Heisenberg, Current Biology 34 (2024) R1230–R1232. corr_author: '1' date_created: 2024-12-15T23:01:49Z date_published: 2024-12-16T00:00:00Z date_updated: 2025-09-09T11:51:15Z day: '16' department: - _id: CaHe doi: 10.1016/j.cub.2024.10.065 external_id: isi: - '001392077000001' pmid: - '39689690' intvolume: ' 34' isi: 1 issue: '24' language: - iso: eng month: '12' oa_version: None page: R1230-R1232 pmid: 1 publication: Current Biology publication_identifier: eissn: - 1879-0445 issn: - 0960-9822 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'Development: Turing mechanics' type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 34 year: '2024' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '18940' abstract: - lang: eng text: BMP signaling has a conserved function in patterning the dorsal-ventral body axis in Bilateria and the directive axis in anthozoan cnidarians. So far, cnidarian studies have focused on the role of different BMP signaling network components in regulating pSMAD1/5 gradient formation. Much less is known about the target genes downstream of BMP signaling. To address this, we generated a genome-wide list of direct pSMAD1/5 target genes in the anthozoan Nematostella vectensis, several of which were conserved in Drosophila and Xenopus. Our ChIP-seq analysis revealed that many of the regulatory molecules with documented bilaterally symmetric expression in Nematostella are directly controlled by BMP signaling. We identified several so far uncharacterized BMP-dependent transcription factors and signaling molecules, whose bilaterally symmetric expression may be indicative of their involvement in secondary axis patterning. One of these molecules is zswim4-6, which encodes a novel nuclear protein that can modulate the pSMAD1/5 gradient and potentially promote BMP-dependent gene repression. acknowledgement: This work was funded by the Austrian Science Foundation (FWF) grants P26962-B21 and P32705-B to GG and by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 637840 [QUANTPATTERN] and 863952 [ACE-OF-SPACE]) to PM. We thank Michaela Schwaiger, Taras Kreslavsky, Hiromi Tagoh, and Patricio Ferrer Murguia for their help with the ChIP protocol, Matthias Richter and Christian Hofer for their assistance with in situ analyses, Emilio Gonzalez Morales for making the measurements for Figure 6—figure supplement 3, Catrin Weiler for the assistance in cloning zebrafish zswim5, David Mörsdorf for critically reading the manuscript and help with data visualization, and the Core Facility for Cell Imaging and Ultrastructure Research of the University of Vienna for access to the confocal microscope. article_processing_charge: Yes article_type: original author: - first_name: Paul full_name: Knabl, Paul last_name: Knabl - first_name: Alexandra full_name: Schauer, Alexandra id: 30A536BA-F248-11E8-B48F-1D18A9856A87 last_name: Schauer orcid: 0000-0001-7659-9142 - first_name: Autumn P full_name: Pomreinke, Autumn P last_name: Pomreinke - first_name: Bob full_name: Zimmermann, Bob last_name: Zimmermann - first_name: Katherine W full_name: Rogers, Katherine W last_name: Rogers - first_name: Daniel full_name: Čapek, Daniel last_name: Čapek - first_name: Patrick full_name: Müller, Patrick last_name: Müller - first_name: Grigory full_name: Genikhovich, Grigory last_name: Genikhovich citation: ama: Knabl P, Schauer A, Pomreinke AP, et al. Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator. eLife. 2024;13. doi:10.7554/elife.80803 apa: Knabl, P., Schauer, A., Pomreinke, A. P., Zimmermann, B., Rogers, K. W., Čapek, D., … Genikhovich, G. (2024). Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.80803 chicago: Knabl, Paul, Alexandra Schauer, Autumn P Pomreinke, Bob Zimmermann, Katherine W Rogers, Daniel Čapek, Patrick Müller, and Grigory Genikhovich. “Analysis of SMAD1/5 Target Genes in a Sea Anemone Reveals ZSWIM4-6 as a Novel BMP Signaling Modulator.” ELife. eLife Sciences Publications, 2024. https://doi.org/10.7554/elife.80803. ieee: P. Knabl et al., “Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator,” eLife, vol. 13. eLife Sciences Publications, 2024. ista: Knabl P, Schauer A, Pomreinke AP, Zimmermann B, Rogers KW, Čapek D, Müller P, Genikhovich G. 2024. Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator. eLife. 13. mla: Knabl, Paul, et al. “Analysis of SMAD1/5 Target Genes in a Sea Anemone Reveals ZSWIM4-6 as a Novel BMP Signaling Modulator.” ELife, vol. 13, eLife Sciences Publications, 2024, doi:10.7554/elife.80803. short: P. Knabl, A. Schauer, A.P. Pomreinke, B. Zimmermann, K.W. Rogers, D. Čapek, P. Müller, G. Genikhovich, ELife 13 (2024). date_created: 2025-01-29T08:48:34Z date_published: 2024-02-07T00:00:00Z date_updated: 2025-01-29T08:56:21Z day: '07' ddc: - '570' department: - _id: CaHe doi: 10.7554/elife.80803 file: - access_level: open_access checksum: 24548a184215d3f4547bba535ccfd7b1 content_type: application/pdf creator: dernst date_created: 2025-01-29T08:50:18Z date_updated: 2025-01-29T08:50:18Z file_id: '18941' file_name: 2024_eLife_Knabl.pdf file_size: 11855972 relation: main_file success: 1 file_date_updated: 2025-01-29T08:50:18Z has_accepted_license: '1' intvolume: ' 13' language: - iso: eng month: '02' oa: 1 oa_version: Published Version publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2024' ... --- _id: '14795' abstract: - lang: eng text: Metazoan development relies on the formation and remodeling of cell-cell contacts. Dynamic reorganization of adhesion receptors and the actomyosin cell cortex in space and time plays a central role in cell-cell contact formation and maturation. Nevertheless, how this process is mechanistically achieved when new contacts are formed remains unclear. Here, by building a biomimetic assay composed of progenitor cells adhering to supported lipid bilayers functionalized with E-cadherin ectodomains, we show that cortical F-actin flows, driven by the depletion of myosin-2 at the cell contact center, mediate the dynamic reorganization of adhesion receptors and cell cortex at the contact. E-cadherin-dependent downregulation of the small GTPase RhoA at the forming contact leads to both a depletion of myosin-2 and a decrease of F-actin at the contact center. At the contact rim, in contrast, myosin-2 becomes enriched by the retraction of bleb-like protrusions, resulting in a cortical tension gradient from the contact rim to its center. This tension gradient, in turn, triggers centrifugal F-actin flows, leading to further accumulation of F-actin at the contact rim and the progressive redistribution of E-cadherin from the contact center to the rim. Eventually, this combination of actomyosin downregulation and flows at the contact determines the characteristic molecular organization, with E-cadherin and F-actin accumulating at the contact rim, where they are needed to mechanically link the contractile cortices of the adhering cells. acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: "We are grateful to Edwin Munro for their feedback and help with the single particle analysis. We thank members of the Heisenberg and Loose labs for their help and feedback on the manuscript, notably Xin Tong for making the PCS2-mCherry-AHPH plasmid. Finally, we thank the Aquatics and Imaging & Optics facilities of ISTA for their continuous support, especially Yann Cesbron for assistance with the laser cutter. This work was supported by an ERC\r\nAdvanced Grant (MECSPEC) to C.-P.H." article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Feyza N full_name: Arslan, Feyza N id: 49DA7910-F248-11E8-B48F-1D18A9856A87 last_name: Arslan orcid: 0000-0001-5809-9566 - 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: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 - 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: Arslan FN, Hannezo EB, Merrin J, Loose M, Heisenberg C-PJ. Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. Current Biology. 2024;34(1):171-182.e8. doi:10.1016/j.cub.2023.11.067 apa: Arslan, F. N., Hannezo, E. B., Merrin, J., Loose, M., & Heisenberg, C.-P. J. (2024). Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. Current Biology. Elsevier. https://doi.org/10.1016/j.cub.2023.11.067 chicago: Arslan, Feyza N, Edouard B Hannezo, Jack Merrin, Martin Loose, and Carl-Philipp J Heisenberg. “Adhesion-Induced Cortical Flows Pattern E-Cadherin-Mediated Cell Contacts.” Current Biology. Elsevier, 2024. https://doi.org/10.1016/j.cub.2023.11.067. ieee: F. N. Arslan, E. B. Hannezo, J. Merrin, M. Loose, and C.-P. J. Heisenberg, “Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts,” Current Biology, vol. 34, no. 1. Elsevier, p. 171–182.e8, 2024. ista: Arslan FN, Hannezo EB, Merrin J, Loose M, Heisenberg C-PJ. 2024. Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts. Current Biology. 34(1), 171–182.e8. mla: Arslan, Feyza N., et al. “Adhesion-Induced Cortical Flows Pattern E-Cadherin-Mediated Cell Contacts.” Current Biology, vol. 34, no. 1, Elsevier, 2024, p. 171–182.e8, doi:10.1016/j.cub.2023.11.067. short: F.N. Arslan, E.B. Hannezo, J. Merrin, M. Loose, C.-P.J. Heisenberg, Current Biology 34 (2024) 171–182.e8. corr_author: '1' date_created: 2024-01-14T23:00:56Z date_published: 2024-01-08T00:00:00Z date_updated: 2025-09-04T11:39:10Z day: '08' ddc: - '570' department: - _id: CaHe - _id: EdHa - _id: MaLo - _id: NanoFab doi: 10.1016/j.cub.2023.11.067 ec_funded: 1 external_id: isi: - '001154500400001' pmid: - '38134934' file: - access_level: open_access checksum: 51220b76d72a614208f84bdbfbaf9b72 content_type: application/pdf creator: dernst date_created: 2024-01-16T10:53:31Z date_updated: 2024-01-16T10:53:31Z file_id: '14813' file_name: 2024_CurrentBiology_Arslan.pdf file_size: 5183861 relation: main_file success: 1 file_date_updated: 2024-01-16T10:53:31Z has_accepted_license: '1' intvolume: ' 34' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 171-182.e8 pmid: 1 project: - _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: Current Biology publication_identifier: eissn: - 1879-0445 issn: - 0960-9822 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 34 year: '2024' ... --- _id: '14846' abstract: - lang: eng text: Contraction and flow of the actin cell cortex have emerged as a common principle by which cells reorganize their cytoplasm and take shape. However, how these cortical flows interact with adjacent cytoplasmic components, changing their form and localization, and how this affects cytoplasmic organization and cell shape remains unclear. Here we show that in ascidian oocytes, the cooperative activities of cortical actomyosin flows and deformation of the adjacent mitochondria-rich myoplasm drive oocyte cytoplasmic reorganization and shape changes following fertilization. We show that vegetal-directed cortical actomyosin flows, established upon oocyte fertilization, lead to both the accumulation of cortical actin at the vegetal pole of the zygote and compression and local buckling of the adjacent elastic solid-like myoplasm layer due to friction forces generated at their interface. Once cortical flows have ceased, the multiple myoplasm buckles resolve into one larger buckle, which again drives the formation of the contraction pole—a protuberance of the zygote’s vegetal pole where maternal mRNAs accumulate. Thus, our findings reveal a mechanism where cortical actomyosin network flows determine cytoplasmic reorganization and cell shape by deforming adjacent cytoplasmic components through friction forces. acknowledged_ssus: - _id: EM-Fac - _id: Bio - _id: NanoFab acknowledgement: We would like to thank A. McDougall, E. Hannezo and the Heisenberg lab for fruitful discussions and reagents. We also thank E. Munro for the iMyo-YFP and Bra>iMyo-mScarlet constructs. This research was supported by the Scientific Service Units of the Institute of Science and Technology Austria through resources provided by the Electron Microscopy Facility, Imaging and Optics Facility and the Nanofabrication Facility. This work was supported by a Joint Project Grant from the FWF (I 3601-B27). article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Silvia full_name: Caballero Mancebo, Silvia id: 2F1E1758-F248-11E8-B48F-1D18A9856A87 last_name: Caballero Mancebo orcid: 0000-0002-5223-3346 - first_name: Rushikesh full_name: Shinde, Rushikesh last_name: Shinde - first_name: Madison full_name: Bolger-Munro, Madison id: 516F03FA-93A3-11EA-A7C5-D6BE3DDC885E last_name: Bolger-Munro orcid: 0000-0002-8176-4824 - first_name: Matilda full_name: Peruzzo, Matilda id: 3F920B30-F248-11E8-B48F-1D18A9856A87 last_name: Peruzzo orcid: 0000-0002-3415-4628 - first_name: Gregory full_name: Szep, Gregory id: 4BFB7762-F248-11E8-B48F-1D18A9856A87 last_name: Szep - first_name: Irene full_name: Steccari, Irene id: 2705C766-9FE2-11EA-B224-C6773DDC885E last_name: Steccari - first_name: David full_name: Labrousse Arias, David id: CD573DF4-9ED3-11E9-9D77-3223E6697425 last_name: Labrousse Arias - first_name: Vanessa full_name: Zheden, Vanessa id: 39C5A68A-F248-11E8-B48F-1D18A9856A87 last_name: Zheden orcid: 0000-0002-9438-4783 - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Andrew full_name: Callan-Jones, Andrew last_name: Callan-Jones - first_name: Raphaël full_name: Voituriez, Raphaël last_name: Voituriez - 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: Caballero Mancebo S, Shinde R, Bolger-Munro M, et al. Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization. Nature Physics. 2024;20:310-321. doi:10.1038/s41567-023-02302-1 apa: Caballero Mancebo, S., Shinde, R., Bolger-Munro, M., Peruzzo, M., Szep, G., Steccari, I., … Heisenberg, C.-P. J. (2024). Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-023-02302-1 chicago: Caballero Mancebo, Silvia, Rushikesh Shinde, Madison Bolger-Munro, Matilda Peruzzo, Gregory Szep, Irene Steccari, David Labrousse Arias, et al. “Friction Forces Determine Cytoplasmic Reorganization and Shape Changes of Ascidian Oocytes upon Fertilization.” Nature Physics. Springer Nature, 2024. https://doi.org/10.1038/s41567-023-02302-1. ieee: S. Caballero Mancebo et al., “Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization,” Nature Physics, vol. 20. Springer Nature, pp. 310–321, 2024. ista: Caballero Mancebo S, Shinde R, Bolger-Munro M, Peruzzo M, Szep G, Steccari I, Labrousse Arias D, Zheden V, Merrin J, Callan-Jones A, Voituriez R, Heisenberg C-PJ. 2024. Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization. Nature Physics. 20, 310–321. mla: Caballero Mancebo, Silvia, et al. “Friction Forces Determine Cytoplasmic Reorganization and Shape Changes of Ascidian Oocytes upon Fertilization.” Nature Physics, vol. 20, Springer Nature, 2024, pp. 310–21, doi:10.1038/s41567-023-02302-1. short: S. Caballero Mancebo, R. Shinde, M. Bolger-Munro, M. Peruzzo, G. Szep, I. Steccari, D. Labrousse Arias, V. Zheden, J. Merrin, A. Callan-Jones, R. Voituriez, C.-P.J. Heisenberg, Nature Physics 20 (2024) 310–321. corr_author: '1' date_created: 2024-01-21T23:00:57Z date_published: 2024-02-01T00:00:00Z date_updated: 2025-09-04T11:48:28Z day: '01' ddc: - '530' department: - _id: CaHe - _id: JoFi - _id: MiSi - _id: EM-Fac - _id: NanoFab doi: 10.1038/s41567-023-02302-1 external_id: isi: - '001138880800005' pmid: - '38370025' file: - access_level: open_access checksum: 7891ebe7c900ae47469ab127031dd1ec content_type: application/pdf creator: dernst date_created: 2024-07-16T12:12:43Z date_updated: 2024-07-16T12:12:43Z file_id: '17267' file_name: 2024_NaturePhysics_CaballeroMancebo.pdf file_size: 9897883 relation: main_file success: 1 file_date_updated: 2024-07-16T12:12:43Z has_accepted_license: '1' intvolume: ' 20' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: 310-321 pmid: 1 project: - _id: 2646861A-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03601 name: Control of embryonic cleavage pattern publication: Nature Physics publication_identifier: eissn: - 1745-2481 issn: - 1745-2473 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/stranger-than-friction-a-force-initiating-life/ scopus_import: '1' status: public title: Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 20 year: '2024' ... --- _id: '15048' abstract: - lang: eng text: Embryogenesis results from the coordinated activities of different signaling pathways controlling cell fate specification and morphogenesis. In vertebrate gastrulation, both Nodal and BMP signaling play key roles in germ layer specification and morphogenesis, yet their interplay to coordinate embryo patterning with morphogenesis is still insufficiently understood. Here, we took a reductionist approach using zebrafish embryonic explants to study the coordination of Nodal and BMP signaling for embryo patterning and morphogenesis. We show that Nodal signaling triggers explant elongation by inducing mesendodermal progenitors but also suppressing BMP signaling activity at the site of mesendoderm induction. Consistent with this, ectopic BMP signaling in the mesendoderm blocks cell alignment and oriented mesendoderm intercalations, key processes during explant elongation. Translating these ex vivo observations to the intact embryo showed that, similar to explants, Nodal signaling suppresses the effect of BMP signaling on cell intercalations in the dorsal domain, thus allowing robust embryonic axis elongation. These findings suggest a dual function of Nodal signaling in embryonic axis elongation by both inducing mesendoderm and suppressing BMP effects in the dorsal portion of the mesendoderm. acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: "We thank Patrick Müller for sharing the chordintt250 mutant zebrafish line as well as the plasmid for chrd-GFP, Katherine Rogers for sharing the bmp2b plasmid and Andrea Pauli for sharing the draculin plasmid. Diana Pinheiro generated the MZlefty1,2;Tg(sebox::EGFP) line. We are grateful to Patrick Müller, Diana Pinheiro and Katherine Rogers and members of the Heisenberg lab for discussions, technical advice and feedback on the manuscript. We also thank Anna Kicheva and Edouard Hannezo for discussions. We thank the Imaging and Optics Facility as well as the Life Science facility at IST Austria for support with microscopy and fish maintenance.\r\nThis work was supported by a European Research Council Advanced Grant\r\n(MECSPEC 742573 to C.-P.H.). A.S. is a recipient of a DOC Fellowship of the Austrian\r\nAcademy of Sciences at IST Austria. Open Access funding provided by Institute of\r\nScience and Technology Austria. " article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Alexandra full_name: Schauer, Alexandra id: 30A536BA-F248-11E8-B48F-1D18A9856A87 last_name: Schauer orcid: 0000-0001-7659-9142 - first_name: Kornelija full_name: Pranjic-Ferscha, Kornelija id: 4362B3C2-F248-11E8-B48F-1D18A9856A87 last_name: Pranjic-Ferscha - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - 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: Schauer A, Pranjic-Ferscha K, Hauschild R, Heisenberg C-PJ. Robust axis elongation by Nodal-dependent restriction of BMP signaling. Development. 2024;151(4):1-18. doi:10.1242/dev.202316 apa: Schauer, A., Pranjic-Ferscha, K., Hauschild, R., & Heisenberg, C.-P. J. (2024). Robust axis elongation by Nodal-dependent restriction of BMP signaling. Development. The Company of Biologists. https://doi.org/10.1242/dev.202316 chicago: Schauer, Alexandra, Kornelija Pranjic-Ferscha, Robert Hauschild, and Carl-Philipp J Heisenberg. “Robust Axis Elongation by Nodal-Dependent Restriction of BMP Signaling.” Development. The Company of Biologists, 2024. https://doi.org/10.1242/dev.202316. ieee: A. Schauer, K. Pranjic-Ferscha, R. Hauschild, and C.-P. J. Heisenberg, “Robust axis elongation by Nodal-dependent restriction of BMP signaling,” Development, vol. 151, no. 4. The Company of Biologists, pp. 1–18, 2024. ista: Schauer A, Pranjic-Ferscha K, Hauschild R, Heisenberg C-PJ. 2024. Robust axis elongation by Nodal-dependent restriction of BMP signaling. Development. 151(4), 1–18. mla: Schauer, Alexandra, et al. “Robust Axis Elongation by Nodal-Dependent Restriction of BMP Signaling.” Development, vol. 151, no. 4, The Company of Biologists, 2024, pp. 1–18, doi:10.1242/dev.202316. short: A. Schauer, K. Pranjic-Ferscha, R. Hauschild, C.-P.J. Heisenberg, Development 151 (2024) 1–18. corr_author: '1' date_created: 2024-03-03T23:00:50Z date_published: 2024-02-01T00:00:00Z date_updated: 2025-09-04T12:10:40Z day: '01' ddc: - '570' department: - _id: CaHe - _id: Bio doi: 10.1242/dev.202316 ec_funded: 1 external_id: isi: - '001170580200001' pmid: - '38372390' file: - access_level: open_access checksum: 6961ea10012bf0d266681f9628bb8f13 content_type: application/pdf creator: dernst date_created: 2024-03-04T07:24:43Z date_updated: 2024-03-04T07:24:43Z file_id: '15050' file_name: 2024_Development_Schauer.pdf file_size: 14839986 relation: main_file success: 1 file_date_updated: 2024-03-04T07:24:43Z has_accepted_license: '1' intvolume: ' 151' isi: 1 issue: '4' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: 1-18 pmid: 1 project: - _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 - _id: 26B1E39C-B435-11E9-9278-68D0E5697425 grant_number: '25239' name: 'Mesendoderm specification in zebrafish: The role of extraembryonic tissues' publication: Development publication_identifier: eissn: - 1477-9129 issn: - 0950-1991 publication_status: published publisher: The Company of Biologists quality_controlled: '1' related_material: record: - id: '14926' relation: research_data status: public scopus_import: '1' status: public title: Robust axis elongation by Nodal-dependent restriction of BMP signaling 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 151 year: '2024' ... --- _id: '15301' abstract: - lang: eng text: Plant morphogenesis relies exclusively on oriented cell expansion and division. Nonetheless, the mechanism(s) determining division plane orientation remain elusive. Here, we studied tissue healing after laser-assisted wounding in roots of Arabidopsis thaliana and uncovered how mechanical forces stabilize and reorient the microtubule cytoskeleton for the orientation of cell division. We identified that root tissue functions as an interconnected cell matrix, with a radial gradient of tissue extendibility causing predictable tissue deformation after wounding. This deformation causes instant redirection of expansion in the surrounding cells and reorientation of microtubule arrays, ultimately predicting cell division orientation. Microtubules are destabilized under low tension, whereas stretching of cells, either through wounding or external aspiration, immediately induces their polymerization. The higher microtubule abundance in the stretched cell parts leads to the reorientation of microtubule arrays and, ultimately, informs cell division planes. This provides a long-sought mechanism for flexible re-arrangement of cell divisions by mechanical forces for tissue reconstruction and plant architecture. acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: We are thankful to Simon Gilroy, Alexander Jones, and Lieven De Veylder for sharing published material. We thank the Imaging & Optics and Life Science Facilities at IST Austria, the Biooptics facility at GMI, and the Cellular Imaging Facility at DBMV UNIL for providing invaluable assistance. The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 742985, from the FWF under the stand-alone grant P29988, and from EMBO (ALTF 253-2023). article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Lukas full_name: Hörmayer, Lukas id: 2EEE7A2A-F248-11E8-B48F-1D18A9856A87 last_name: Hörmayer orcid: 0000-0001-8295-2926 - first_name: Juan C full_name: Montesinos López, Juan C id: 310A8E3E-F248-11E8-B48F-1D18A9856A87 last_name: Montesinos López orcid: 0000-0001-9179-6099 - first_name: N full_name: Trozzi, N last_name: Trozzi - first_name: Leonhard full_name: Spona, Leonhard id: b52391fb-f636-11ee-939c-8a8c47552e8a last_name: Spona - first_name: Saiko full_name: Yoshida, Saiko id: 2E46069C-F248-11E8-B48F-1D18A9856A87 last_name: Yoshida - first_name: Petra full_name: Marhavá, Petra id: 44E59624-F248-11E8-B48F-1D18A9856A87 last_name: Marhavá - first_name: Silvia full_name: Caballero Mancebo, Silvia id: 2F1E1758-F248-11E8-B48F-1D18A9856A87 last_name: Caballero Mancebo orcid: 0000-0002-5223-3346 - first_name: Eva full_name: Benková, Eva id: 38F4F166-F248-11E8-B48F-1D18A9856A87 last_name: Benková orcid: 0000-0002-8510-9739 - 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 - first_name: Y full_name: Dagdas, Y last_name: Dagdas - first_name: M full_name: Majda, M last_name: Majda - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Hörmayer L, Montesinos López JC, Trozzi N, et al. Mechanical forces in plant tissue matrix orient cell divisions via microtubule stabilization. Developmental Cell. 2024;59(10):1333-1344.e4. doi:10.1016/j.devcel.2024.03.009 apa: Hörmayer, L., Montesinos López, J. C., Trozzi, N., Spona, L., Yoshida, S., Marhavá, P., … Friml, J. (2024). Mechanical forces in plant tissue matrix orient cell divisions via microtubule stabilization. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2024.03.009 chicago: Hörmayer, Lukas, Juan C Montesinos López, N Trozzi, Leonhard Spona, Saiko Yoshida, Petra Marhavá, Silvia Caballero Mancebo, et al. “Mechanical Forces in Plant Tissue Matrix Orient Cell Divisions via Microtubule Stabilization.” Developmental Cell. Elsevier, 2024. https://doi.org/10.1016/j.devcel.2024.03.009. ieee: L. Hörmayer et al., “Mechanical forces in plant tissue matrix orient cell divisions via microtubule stabilization,” Developmental Cell, vol. 59, no. 10. Elsevier, p. 1333–1344.e4, 2024. ista: Hörmayer L, Montesinos López JC, Trozzi N, Spona L, Yoshida S, Marhavá P, Caballero Mancebo S, Benková E, Heisenberg C-PJ, Dagdas Y, Majda M, Friml J. 2024. Mechanical forces in plant tissue matrix orient cell divisions via microtubule stabilization. Developmental Cell. 59(10), 1333–1344.e4. mla: Hörmayer, Lukas, et al. “Mechanical Forces in Plant Tissue Matrix Orient Cell Divisions via Microtubule Stabilization.” Developmental Cell, vol. 59, no. 10, Elsevier, 2024, p. 1333–1344.e4, doi:10.1016/j.devcel.2024.03.009. short: L. Hörmayer, J.C. Montesinos López, N. Trozzi, L. Spona, S. Yoshida, P. Marhavá, S. Caballero Mancebo, E. Benková, C.-P.J. Heisenberg, Y. Dagdas, M. Majda, J. Friml, Developmental Cell 59 (2024) 1333–1344.e4. corr_author: '1' date_created: 2024-04-08T12:07:57Z date_published: 2024-05-20T00:00:00Z date_updated: 2025-09-04T13:32:08Z day: '20' ddc: - '570' department: - _id: JiFr - _id: EvBe - _id: CaHe doi: 10.1016/j.devcel.2024.03.009 ec_funded: 1 external_id: isi: - '001301584600001' pmid: - '38579717' file: - access_level: open_access checksum: 22b374fb50a40d380b7686c84258d271 content_type: application/pdf creator: dernst date_created: 2024-08-20T11:22:16Z date_updated: 2024-08-20T11:22:16Z file_id: '17452' file_name: 2024_DevelopmentalCell_Hoermayer.pdf file_size: 5195262 relation: main_file success: 1 file_date_updated: 2024-08-20T11:22:16Z has_accepted_license: '1' intvolume: ' 59' isi: 1 issue: '10' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 1333-1344.e4 pmid: 1 project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants - _id: 262EF96E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29988 name: RNA-directed DNA methylation in plant development publication: Developmental Cell publication_identifier: eissn: - 1878-1551 issn: - 1534-5807 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA website relation: press_release url: https://ista.ac.at/en/news/how-plants-heal-wounds/ scopus_import: '1' status: public title: Mechanical forces in plant tissue matrix orient cell divisions via microtubule stabilization 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 59 year: '2024' ... --- _id: '14041' abstract: - lang: eng text: Tissue morphogenesis and patterning during development involve the segregation of cell types. Segregation is driven by differential tissue surface tensions generated by cell types through controlling cell-cell contact formation by regulating adhesion and actomyosin contractility-based cellular cortical tensions. We use vertebrate tissue cell types and zebrafish germ layer progenitors as in vitro models of 3-dimensional heterotypic segregation and developed a quantitative analysis of their dynamics based on 3D time-lapse microscopy. We show that general inhibition of actomyosin contractility by the Rho kinase inhibitor Y27632 delays segregation. Cell type-specific inhibition of non-muscle myosin2 activity by overexpression of myosin assembly inhibitor S100A4 reduces tissue surface tension, manifested in decreased compaction during aggregation and inverted geometry observed during segregation. The same is observed when we express a constitutively active Rho kinase isoform to ubiquitously keep actomyosin contractility high at cell-cell and cell-medium interfaces and thus overriding the interface-specific regulation of cortical tensions. Tissue surface tension regulation can become an effective tool in tissue engineering. acknowledgement: "We thank Marton Gulyas (ELTE Eötvös University) for development of videomicroscopy experiment manager and image analysis software. Authors are grateful to Gabor Forgacs (University of Missouri) for critical reading of earlier versions of this manuscript as well as to Zsuzsa Akos and Andras Czirok (ELTE Eötvös University) for fruitful discussions. This work was supported by EU FP7, ERC COLLMOT Project No 227878 to TV, the National Research Development and Innovation Fund of Hungary, K119359 and also Project No 2018-1.2.1-NKP-2018-00005 to LN. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 955576. MV was supported by the Ja´nos Bolyai Fellowship of the Hungarian Academy of Sciences.\r\nOpen access funding provided by Eötvös Loránd University." article_number: '817' article_processing_charge: Yes article_type: original author: - first_name: Elod full_name: Méhes, Elod last_name: Méhes - first_name: Enys full_name: Mones, Enys last_name: Mones - first_name: Máté full_name: Varga, Máté last_name: Varga - first_name: Áron full_name: Zsigmond, Áron last_name: Zsigmond - first_name: Beáta full_name: Biri-Kovács, Beáta last_name: Biri-Kovács - first_name: László full_name: Nyitray, László last_name: Nyitray - first_name: Vanessa full_name: Barone, Vanessa id: 419EECCC-F248-11E8-B48F-1D18A9856A87 last_name: Barone orcid: 0000-0003-2676-3367 - first_name: Gabriel full_name: Krens, Gabriel id: 2B819732-F248-11E8-B48F-1D18A9856A87 last_name: Krens orcid: 0000-0003-4761-5996 - 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 - first_name: Tamás full_name: Vicsek, Tamás last_name: Vicsek citation: ama: Méhes E, Mones E, Varga M, et al. 3D cell segregation geometry and dynamics are governed by tissue surface tension regulation. Communications Biology. 2023;6. doi:10.1038/s42003-023-05181-7 apa: Méhes, E., Mones, E., Varga, M., Zsigmond, Á., Biri-Kovács, B., Nyitray, L., … Vicsek, T. (2023). 3D cell segregation geometry and dynamics are governed by tissue surface tension regulation. Communications Biology. Springer Nature. https://doi.org/10.1038/s42003-023-05181-7 chicago: Méhes, Elod, Enys Mones, Máté Varga, Áron Zsigmond, Beáta Biri-Kovács, László Nyitray, Vanessa Barone, Gabriel Krens, Carl-Philipp J Heisenberg, and Tamás Vicsek. “3D Cell Segregation Geometry and Dynamics Are Governed by Tissue Surface Tension Regulation.” Communications Biology. Springer Nature, 2023. https://doi.org/10.1038/s42003-023-05181-7. ieee: E. Méhes et al., “3D cell segregation geometry and dynamics are governed by tissue surface tension regulation,” Communications Biology, vol. 6. Springer Nature, 2023. ista: Méhes E, Mones E, Varga M, Zsigmond Á, Biri-Kovács B, Nyitray L, Barone V, Krens G, Heisenberg C-PJ, Vicsek T. 2023. 3D cell segregation geometry and dynamics are governed by tissue surface tension regulation. Communications Biology. 6, 817. mla: Méhes, Elod, et al. “3D Cell Segregation Geometry and Dynamics Are Governed by Tissue Surface Tension Regulation.” Communications Biology, vol. 6, 817, Springer Nature, 2023, doi:10.1038/s42003-023-05181-7. short: E. Méhes, E. Mones, M. Varga, Á. Zsigmond, B. Biri-Kovács, L. Nyitray, V. Barone, G. Krens, C.-P.J. Heisenberg, T. Vicsek, Communications Biology 6 (2023). date_created: 2023-08-13T22:01:13Z date_published: 2023-08-04T00:00:00Z date_updated: 2023-12-13T12:07:33Z day: '04' ddc: - '570' department: - _id: CaHe - _id: Bio doi: 10.1038/s42003-023-05181-7 external_id: isi: - '001042544100001' pmid: - '37542157' file: - access_level: open_access checksum: 1f9324f736bdbb76426b07736651c4cd content_type: application/pdf creator: dernst date_created: 2023-08-14T07:17:36Z date_updated: 2023-08-14T07:17:36Z file_id: '14045' file_name: 2023_CommBiology_Mehes.pdf file_size: 10181997 relation: main_file success: 1 file_date_updated: 2023-08-14T07:17:36Z has_accepted_license: '1' intvolume: ' 6' isi: 1 language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Communications Biology publication_identifier: eissn: - 2399-3642 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: 3D cell segregation geometry and dynamics are governed by tissue surface tension regulation 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 6 year: '2023' ... --- _id: '14080' abstract: - lang: eng text: Extracellular signal-regulated kinase (ERK) has been recognized as a critical regulator in various physiological and pathological processes. Extensive research has elucidated the signaling mechanisms governing ERK activation via biochemical regulations with upstream molecules, particularly receptor tyrosine kinases (RTKs). However, recent advances have highlighted the role of mechanical forces in activating the RTK–ERK signaling pathways, thereby opening new avenues of research into mechanochemical interplay in multicellular tissues. Here, we review the force-induced ERK activation in cells and propose possible mechanosensing mechanisms underlying the mechanoresponsive ERK activation. We conclude that mechanical forces are not merely passive factors shaping cells and tissues but also active regulators of cellular signaling pathways controlling collective cell behaviors. acknowledgement: TH was supported by JSPS KAKENHI Grant (no. 21H05290) and the Ministry of Education under the Research Centres of Excellence programme through the Mechanobiology Institute at National University of Singapore and by Department of Physiology at National University of Singapore. NH was supported by JSPS KAKENHI Grant (no. 20K22653). KA was supported by JSPS KAKENHI Grants (no. 19H05798 and no. 22H02625). MM was supported by JSPS KAKENHI Grants (no. 19H00993 and no. 20H05898) and JST Moonshot R&D Grant JPMJPS2022. We appreciate Virgile Viasnoff and the lab members for their valuable comments on the manuscript. We apologize to authors whose work could not be highlighted due to space limitations. article_number: '102217' article_processing_charge: Yes (in subscription journal) article_type: review author: - first_name: Tsuyoshi full_name: Hirashima, Tsuyoshi last_name: Hirashima - first_name: Naoya full_name: Hino, Naoya id: 5299a9ce-7679-11eb-a7bc-d1e62b936307 last_name: Hino - first_name: Kazuhiro full_name: Aoki, Kazuhiro last_name: Aoki - first_name: Michiyuki full_name: Matsuda, Michiyuki last_name: Matsuda citation: ama: Hirashima T, Hino N, Aoki K, Matsuda M. Stretching the limits of extracellular signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation. Current Opinion in Cell Biology. 2023;84(10). doi:10.1016/j.ceb.2023.102217 apa: Hirashima, T., Hino, N., Aoki, K., & Matsuda, M. (2023). Stretching the limits of extracellular signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation. Current Opinion in Cell Biology. Elsevier. https://doi.org/10.1016/j.ceb.2023.102217 chicago: Hirashima, Tsuyoshi, Naoya Hino, Kazuhiro Aoki, and Michiyuki Matsuda. “Stretching the Limits of Extracellular Signal-Related Kinase (ERK) Signaling — Cell Mechanosensing to ERK Activation.” Current Opinion in Cell Biology. Elsevier, 2023. https://doi.org/10.1016/j.ceb.2023.102217. ieee: T. Hirashima, N. Hino, K. Aoki, and M. Matsuda, “Stretching the limits of extracellular signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation,” Current Opinion in Cell Biology, vol. 84, no. 10. Elsevier, 2023. ista: Hirashima T, Hino N, Aoki K, Matsuda M. 2023. Stretching the limits of extracellular signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation. Current Opinion in Cell Biology. 84(10), 102217. mla: Hirashima, Tsuyoshi, et al. “Stretching the Limits of Extracellular Signal-Related Kinase (ERK) Signaling — Cell Mechanosensing to ERK Activation.” Current Opinion in Cell Biology, vol. 84, no. 10, 102217, Elsevier, 2023, doi:10.1016/j.ceb.2023.102217. short: T. Hirashima, N. Hino, K. Aoki, M. Matsuda, Current Opinion in Cell Biology 84 (2023). date_created: 2023-08-20T22:01:12Z date_published: 2023-10-01T00:00:00Z date_updated: 2024-01-30T12:52:42Z day: '01' ddc: - '570' department: - _id: CaHe doi: 10.1016/j.ceb.2023.102217 external_id: isi: - '001054692200001' pmid: - '37574635' file: - access_level: open_access checksum: 25923f8ae71344e8974530dd23c71bdc content_type: application/pdf creator: dernst date_created: 2024-01-30T12:52:12Z date_updated: 2024-01-30T12:52:12Z file_id: '14909' file_name: 2023_CurrentOpinionCellBio_Hirashima.pdf file_size: 1173762 relation: main_file success: 1 file_date_updated: 2024-01-30T12:52:12Z has_accepted_license: '1' intvolume: ' 84' isi: 1 issue: '10' language: - iso: eng month: '10' oa: 1 oa_version: Published Version pmid: 1 publication: Current Opinion in Cell Biology publication_identifier: eissn: - 1879-0410 issn: - 0955-0674 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Stretching the limits of extracellular signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 84 year: '2023' ... --- OA_place: publisher OA_type: free access _id: '14082' abstract: - lang: eng text: Epithelial barrier function is commonly analyzed using transepithelial electrical resistance, which measures ion flux across a monolayer, or by adding traceable macromolecules and monitoring their passage across the monolayer. Although these methods measure changes in global barrier function, they lack the sensitivity needed to detect local or transient barrier breaches, and they do not reveal the location of barrier leaks. Therefore, we previously developed a method that we named the zinc-based ultrasensitive microscopic barrier assay (ZnUMBA), which overcomes these limitations, allowing for detection of local tight junction leaks with high spatiotemporal resolution. Here, we present expanded applications for ZnUMBA. ZnUMBA can be used in Xenopus embryos to measure the dynamics of barrier restoration and actin accumulation following laser injury. ZnUMBA can also be effectively utilized in developing zebrafish embryos as well as cultured monolayers of Madin–Darby canine kidney (MDCK) II epithelial cells. ZnUMBA is a powerful and flexible method that, with minimal optimization, can be applied to multiple systems to measure dynamic changes in barrier function with spatiotemporal precision. acknowledged_ssus: - _id: PreCl - _id: Bio acknowledgement: "The authors thank their respective lab members for feedback and helpful discussions. We thank the bioimaging and zebrafish facilities of IST Austria for their support.\r\nThis work was supported by the National Institutes of Health [R01GM112794 to A.L.M.], by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science [21K06156 to T.H.], by the Grant Program for Biomedical Engineering Research from the Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering [to T.H.] and by funding from the European Research Council [advanced grant 742573 to C.-P.H.]. " article_number: jcs260668 article_processing_charge: No article_type: original author: - first_name: Tomohito full_name: Higashi, Tomohito last_name: Higashi - first_name: Rachel E. full_name: Stephenson, Rachel E. last_name: Stephenson - first_name: Cornelia full_name: Schwayer, Cornelia id: 3436488C-F248-11E8-B48F-1D18A9856A87 last_name: Schwayer orcid: 0000-0001-5130-2226 - first_name: Karla full_name: Huljev, Karla id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87 last_name: Huljev - first_name: Atsuko Y. full_name: Higashi, Atsuko Y. last_name: Higashi - 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 - first_name: Hideki full_name: Chiba, Hideki last_name: Chiba - first_name: Ann L. full_name: Miller, Ann L. last_name: Miller citation: ama: Higashi T, Stephenson RE, Schwayer C, et al. ZnUMBA - a live imaging method to detect local barrier breaches. Journal of Cell Science. 2023;136(15). doi:10.1242/jcs.260668 apa: Higashi, T., Stephenson, R. E., Schwayer, C., Huljev, K., Higashi, A. Y., Heisenberg, C.-P. J., … Miller, A. L. (2023). ZnUMBA - a live imaging method to detect local barrier breaches. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.260668 chicago: Higashi, Tomohito, Rachel E. Stephenson, Cornelia Schwayer, Karla Huljev, Atsuko Y. Higashi, Carl-Philipp J Heisenberg, Hideki Chiba, and Ann L. Miller. “ZnUMBA - a Live Imaging Method to Detect Local Barrier Breaches.” Journal of Cell Science. The Company of Biologists, 2023. https://doi.org/10.1242/jcs.260668. ieee: T. Higashi et al., “ZnUMBA - a live imaging method to detect local barrier breaches,” Journal of Cell Science, vol. 136, no. 15. The Company of Biologists, 2023. ista: Higashi T, Stephenson RE, Schwayer C, Huljev K, Higashi AY, Heisenberg C-PJ, Chiba H, Miller AL. 2023. ZnUMBA - a live imaging method to detect local barrier breaches. Journal of Cell Science. 136(15), jcs260668. mla: Higashi, Tomohito, et al. “ZnUMBA - a Live Imaging Method to Detect Local Barrier Breaches.” Journal of Cell Science, vol. 136, no. 15, jcs260668, The Company of Biologists, 2023, doi:10.1242/jcs.260668. short: T. Higashi, R.E. Stephenson, C. Schwayer, K. Huljev, A.Y. Higashi, C.-P.J. Heisenberg, H. Chiba, A.L. Miller, Journal of Cell Science 136 (2023). date_created: 2023-08-20T22:01:13Z date_published: 2023-08-01T00:00:00Z date_updated: 2025-06-25T06:28:45Z day: '01' ddc: - '570' department: - _id: CaHe - _id: EvBe doi: 10.1242/jcs.260668 ec_funded: 1 external_id: isi: - '001070149000001' pmid: - '37461809' has_accepted_license: '1' intvolume: ' 136' isi: 1 issue: '15' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1242/jcs.260668 month: '08' oa: 1 oa_version: None pmid: 1 project: - _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: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - 0021-9533 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: ZnUMBA - a live imaging method to detect local barrier breaches type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 136 year: '2023' ... --- _id: '12830' abstract: - lang: eng text: Interstitial fluid (IF) accumulation between embryonic cells is thought to be important for embryo patterning and morphogenesis. Here, we identify a positive mechanical feedback loop between cell migration and IF relocalization and find that it promotes embryonic axis formation during zebrafish gastrulation. We show that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between the yolk cell and deep cell tissue to extend the embryonic axis, compress the overlying deep cell layer, thereby causing IF to flow from the deep cell layer to the boundary between the yolk cell and the deep cell layer, directly ahead of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion formation and migration by opening up the space into which the ppl moves and, thereby, the ability of the ppl to trigger IF relocalization by pushing against the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic feedback loop between cell migration and IF relocalization. acknowledged_ssus: - _id: PreCl - _id: Bio acknowledgement: We thank Andrea Pauli (IMP) and Edouard Hannezo (ISTA) for fruitful discussions and support with the SPIM experiments; the Heisenberg group, and especially Feyza Nur Arslan and Alexandra Schauer, for discussions and feedback; Michaela Jović (ISTA) for help with the quantitative real-time PCR protocol; the bioimaging and zebrafish facilities of ISTA for continuous support; Stephan Preibisch (Janelia Research Campus) for support with the SPIM data analysis; and Nobuhiro Nakamura (Tokyo Institute of Technology) for sharing α1-Na+/K+-ATPase antibody. This work was supported by funding from the European Union (European Research Council Advanced grant 742573 to C.-P.H.), postdoctoral fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P., and a PhD fellowship from the Studienstiftung des deutschen Volkes to F.P. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Karla full_name: Huljev, Karla id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87 last_name: Huljev - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour - 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: Friedrich full_name: Preusser, Friedrich last_name: Preusser - first_name: Irene full_name: Steccari, Irene id: 2705C766-9FE2-11EA-B224-C6773DDC885E last_name: Steccari - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Suyash full_name: Naik, Suyash id: 2C0B105C-F248-11E8-B48F-1D18A9856A87 last_name: Naik orcid: 0000-0001-8421-5508 - 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: Huljev K, Shamipour S, Nunes Pinheiro DC, et al. A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. Developmental Cell. 2023;58(7):582-596.e7. doi:10.1016/j.devcel.2023.02.016 apa: Huljev, K., Shamipour, S., Nunes Pinheiro, D. C., Preusser, F., Steccari, I., Sommer, C. M., … Heisenberg, C.-P. J. (2023). A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2023.02.016 chicago: Huljev, Karla, Shayan Shamipour, Diana C Nunes Pinheiro, Friedrich Preusser, Irene Steccari, Christoph M Sommer, Suyash Naik, and Carl-Philipp J Heisenberg. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” Developmental Cell. Elsevier, 2023. https://doi.org/10.1016/j.devcel.2023.02.016. ieee: K. Huljev et al., “A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish,” Developmental Cell, vol. 58, no. 7. Elsevier, p. 582–596.e7, 2023. ista: Huljev K, Shamipour S, Nunes Pinheiro DC, Preusser F, Steccari I, Sommer CM, Naik S, Heisenberg C-PJ. 2023. A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish. Developmental Cell. 58(7), 582–596.e7. mla: Huljev, Karla, et al. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” Developmental Cell, vol. 58, no. 7, Elsevier, 2023, p. 582–596.e7, doi:10.1016/j.devcel.2023.02.016. short: K. Huljev, S. Shamipour, D.C. Nunes Pinheiro, F. Preusser, I. Steccari, C.M. Sommer, S. Naik, C.-P.J. Heisenberg, Developmental Cell 58 (2023) 582–596.e7. corr_author: '1' date_created: 2023-04-16T22:01:07Z date_published: 2023-04-10T00:00:00Z date_updated: 2025-04-23T08:51:34Z day: '10' ddc: - '570' department: - _id: CaHe - _id: Bio doi: 10.1016/j.devcel.2023.02.016 ec_funded: 1 external_id: isi: - '000982111800001' pmid: - '36931269' file: - access_level: open_access checksum: c80ca2ebc241232aacdb5aa4b4c80957 content_type: application/pdf creator: dernst date_created: 2023-04-17T07:41:25Z date_updated: 2023-04-17T07:41:25Z file_id: '12842' file_name: 2023_DevelopmentalCell_Huljev.pdf file_size: 7925886 relation: main_file success: 1 file_date_updated: 2023-04-17T07:41:25Z has_accepted_license: '1' intvolume: ' 58' isi: 1 issue: '7' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: 582-596.e7 pmid: 1 project: - _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 - _id: 26520D1E-B435-11E9-9278-68D0E5697425 grant_number: ALTF 850-2017 name: Coordination of mesendoderm cell fate specification and internalization during zebrafish gastrulation - _id: 266BC5CE-B435-11E9-9278-68D0E5697425 grant_number: LT000429 name: Coordination of mesendoderm fate specification and internalization during zebrafish gastrulation publication: Developmental Cell publication_identifier: eissn: - 1878-1551 issn: - 1534-5807 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 58 year: '2023' ...