--- 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 fulldoi: https://doi.org/10.1038/s41567-025-03122-1 has_accepted_license: '1' intvolume: ' 22' language: - iso: eng 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 _id: '22804' abstract: - lang: eng text: 'Embryo cleavage — a series of rapid, reductive cell divisions — is the first morphogenetic movement following fertilisation. It lays the foundation for subsequent developmental events, including gastrulation, germ layer specification, organogenesis, and the establishment of the overall body plan. Two major modes of cleavage exist in the animal kingdom: holoblastic (complete) and meroblastic (incomplete) cleavage. Because holoblastic cleavage resembles canonical cytokinesis, its biochemical and mechanical basis has been extensively studied — an annular contractile ring forms at the equator and constricts in a purse-string-like manner, leading to the complete separation of two daughter cells. In contrast, although meroblastic cleavage occurs widely across the animal kingdom (e.g. in fish, reptiles, birds, and cephalopod molluscs), its mechanical basis remains largely unclear. During meroblastic cleavage, the cytokinetic furrow forms only at one pole and does not traverse the entire embryo, raising the question of how cytokinesis proceeds in the absence of a closed contractile ring. Moreover, the resulting daughter cells are not fully separated from the underlying yolk compartment, and how these blastomeres are subsequently cellularised remains unknown. This thesis takes the zebrafish as a model organism to address both questions. The first part characterises the biochemical and mechanical mechanisms underlying non-canonical meroblastic cleavage, revealing a two-phase process in which actomyosin cable contraction and cadherin-mediated membrane adhesion act sequentially to drive furrow ingression and invagination. The second part sheds light on the spatiotemporal dynamics by which individual blastomeres become cellularised, and uncovers a previously unrecognised contribution of central blastomeres to the yolk syncytial layer.' acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: "I gratefully acknowledge the NOMIS Stiftung (Project ID 5061.844, Cytoplasmic\r\nself-organization into cell-like compartments as a common guiding principle in\r\nearly animal development) for funding my doctoral studies." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Xin full_name: Tong, Xin id: 50F65CDC-AA30-11E9-A72B-8A12E6697425 last_name: Tong citation: ama: Tong X. Towards a deeper understanding of meroblastic cleavage. 2026. doi:10.15479/AT-ISTA-22804 apa: Tong, X. (2026). Towards a deeper understanding of meroblastic cleavage. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-22804 chicago: Tong, Xin. “Towards a Deeper Understanding of Meroblastic Cleavage.” Institute of Science and Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-22804. ieee: X. Tong, “Towards a deeper understanding of meroblastic cleavage,” Institute of Science and Technology Austria, 2026. ista: Tong X. 2026. Towards a deeper understanding of meroblastic cleavage. Institute of Science and Technology Austria. mla: Tong, Xin. Towards a Deeper Understanding of Meroblastic Cleavage. Institute of Science and Technology Austria, 2026, doi:10.15479/AT-ISTA-22804. short: X. Tong, Towards a Deeper Understanding of Meroblastic Cleavage, Institute of Science and Technology Austria, 2026. corr_author: '1' date_created: 2026-09-04T11:54:20Z date_published: 2026-07-12T00:00:00Z date_updated: 2026-10-05T08:56:10Z day: '12' ddc: - '596' - '532' - '572' degree_awarded: PhD department: - _id: GradSch - _id: CaHe doi: 10.15479/AT-ISTA-22804 doi_confirm: '1' file: - access_level: closed checksum: fdcc187a5a92e785da0eff8936fb127e content_type: application/zip creator: xtong date_created: 2026-09-11T13:04:37Z date_updated: 2026-09-14T08:28:06Z file_id: '22909' file_name: 2026_TONG_Xin_Thesis.zip file_size: 126983933 relation: source_file - access_level: open_access checksum: 23ee39b3f08bccd46acfd332e67f5232 content_type: application/pdf creator: xtong date_created: 2026-09-14T12:30:07Z date_updated: 2026-09-14T12:48:53Z file_id: '22930' file_name: 2026_TONG_Xin_Thesis.pdf file_size: 46855054 relation: main_file file_date_updated: 2026-09-14T12:48:53Z fulldoi: https://doi.org/10.15479/AT-ISTA-22804 has_accepted_license: '1' keyword: - meroblastic cleavage - cytokinesis - active gel theory - embryogenesis - zebrafish - adhesion language: - iso: eng license: https://creativecommons.org/licenses/by-nc/4.0/ month: '07' oa: 1 oa_version: Published Version page: '121' project: - _id: 917c023a-16d5-11f0-9cad-eb5cafc52090 name: Cytoplasmic self-organization into cell-like compartments as a common guiding principle in early animal development publication_identifier: isbn: - 978-3-99078-080-0 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '22777' relation: research_data status: public - id: '22807' relation: part_of_dissertation status: public researchdata_availability: upon request 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 title: Towards a deeper understanding of meroblastic cleavage 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: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2026' ...