[{"citation":{"mla":"Mishra, Nikhil, et al. “Geometry-Driven Asymmetric Cell Divisions Pattern Cell Cycles and Zygotic Genome Activation in the Zebrafish Embryo.” <i>Nature Physics</i>, vol. 22, Springer Nature, 2026, pp. 139–50, doi:<a href=\"https://doi.org/10.1038/s41567-025-03122-1\">10.1038/s41567-025-03122-1</a>.","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,” <i>Nature Physics</i>, vol. 22. Springer Nature, pp. 139–150, 2026.","apa":"Mishra, N., Li, Y. I., Hannezo, E. B., &#38; Heisenberg, C.-P. J. (2026). Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-025-03122-1\">https://doi.org/10.1038/s41567-025-03122-1</a>","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. <i>Nature Physics</i>. 2026;22:139-150. doi:<a href=\"https://doi.org/10.1038/s41567-025-03122-1\">10.1038/s41567-025-03122-1</a>","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.” <i>Nature Physics</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41567-025-03122-1\">https://doi.org/10.1038/s41567-025-03122-1</a>.","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.","short":"N. Mishra, Y.I. Li, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 22 (2026) 139–150."},"ddc":["570"],"intvolume":"        22","doi":"10.1038/s41567-025-03122-1","author":[{"full_name":"Mishra, Nikhil","first_name":"Nikhil","id":"C4D70E82-1081-11EA-B3ED-9A4C3DDC885E","orcid":"0000-0002-6425-5788","last_name":"Mishra"},{"id":"ee7a5ca8-8b71-11ed-b662-b3341c05b7eb","last_name":"Li","first_name":"Yuting I","full_name":"Li, Yuting I"},{"full_name":"Hannezo, Edouard B","first_name":"Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J"}],"publisher":"Springer Nature","has_accepted_license":"1","file_date_updated":"2026-01-21T08:21:11Z","department":[{"_id":"EdHa"},{"_id":"CaHe"}],"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."}],"article_processing_charge":"Yes (via OA deal)","date_updated":"2026-04-28T12:55:30Z","publication_status":"published","ec_funded":1,"month":"01","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"},{"call_identifier":"H2020","grant_number":"101034413","name":"IST-BRIDGE: International postdoctoral program","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c"},{"name":"Cytoplasmic self-organization into cell-like compartments as a common guiding principle in early animal development","_id":"917c023a-16d5-11f0-9cad-eb5cafc52090"}],"external_id":{"oaworkid":["W7118187193"]},"quality_controlled":"1","status":"public","OA_place":"publisher","date_created":"2026-01-20T10:12:19Z","OA_type":"hybrid","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"},{"_id":"LifeSc"}],"PlanS_conform":"1","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).","volume":22,"file":[{"file_name":"2026_NaturePhysics_Mishra.pdf","relation":"main_file","date_updated":"2026-01-21T08:21:11Z","file_id":"21026","access_level":"open_access","checksum":"0ab7ac2fbcb61a364dba57152db64ed7","content_type":"application/pdf","file_size":7335694,"creator":"dernst","success":1,"date_created":"2026-01-21T08:21:11Z"}],"type":"journal_article","article_type":"original","_id":"21015","oa_version":"Published Version","year":"2026","fulldoi":"https://doi.org/10.1038/s41567-025-03122-1","date_published":"2026-01-05T00:00:00Z","oa":1,"publication_identifier":{"issnl":[" 1745-2473"],"issn":["1745-2473"],"eissn":["1745-2481"]},"scopus_import":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"page":"139-150","corr_author":"1","related_material":{"link":[{"relation":"research_data","description":"News on ISTA website","url":"https://ista.ac.at/en/news/geometry-shapes-life/"}]},"oaworkid":1,"publication":"Nature Physics","title":"Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo","day":"05"},{"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"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.","type":"dissertation","file":[{"access_level":"closed","checksum":"fdcc187a5a92e785da0eff8936fb127e","content_type":"application/zip","file_size":126983933,"creator":"xtong","file_name":"2026_TONG_Xin_Thesis.zip","relation":"source_file","date_updated":"2026-09-14T08:28:06Z","file_id":"22909","date_created":"2026-09-11T13:04:37Z"},{"content_type":"application/pdf","checksum":"23ee39b3f08bccd46acfd332e67f5232","access_level":"open_access","creator":"xtong","file_size":46855054,"file_name":"2026_TONG_Xin_Thesis.pdf","relation":"main_file","file_id":"22930","date_updated":"2026-09-14T12:48:53Z","date_created":"2026-09-14T12:30:07Z"}],"keyword":["meroblastic cleavage","cytokinesis","active gel theory","embryogenesis","zebrafish","adhesion"],"supervisor":[{"first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87"}],"year":"2026","_id":"22804","oa_version":"Published Version","date_published":"2026-07-12T00:00:00Z","fulldoi":"https://doi.org/10.15479/AT-ISTA-22804","degree_awarded":"PhD","oa":1,"publication_identifier":{"isbn":["978-3-99078-080-0"],"issn":["2663-337X"]},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","page":"121","corr_author":"1","related_material":{"record":[{"id":"22777","relation":"research_data","status":"public"},{"id":"22807","relation":"part_of_dissertation","status":"public"}]},"tmp":{"short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png"},"researchdata_availability":"upon request","title":"Towards a deeper understanding of meroblastic cleavage","alternative_title":["ISTA Thesis"],"day":"12","citation":{"short":"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. <i>Towards a Deeper Understanding of Meroblastic Cleavage</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22804\">10.15479/AT-ISTA-22804</a>.","ieee":"X. Tong, “Towards a deeper understanding of meroblastic cleavage,” Institute of Science and Technology Austria, 2026.","apa":"Tong, X. (2026). <i>Towards a deeper understanding of meroblastic cleavage</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-22804\">https://doi.org/10.15479/AT-ISTA-22804</a>","ama":"Tong X. Towards a deeper understanding of meroblastic cleavage. 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22804\">10.15479/AT-ISTA-22804</a>","chicago":"Tong, Xin. “Towards a Deeper Understanding of Meroblastic Cleavage.” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-22804\">https://doi.org/10.15479/AT-ISTA-22804</a>."},"ddc":["596","532","572"],"doi":"10.15479/AT-ISTA-22804","author":[{"last_name":"Tong","id":"50F65CDC-AA30-11E9-A72B-8A12E6697425","first_name":"Xin","full_name":"Tong, Xin"}],"publisher":"Institute of Science and Technology Austria","has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"CaHe"}],"file_date_updated":"2026-09-14T12:48:53Z","article_processing_charge":"No","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."}],"date_updated":"2026-10-05T08:56:10Z","publication_status":"published","month":"07","project":[{"name":"Cytoplasmic self-organization into cell-like compartments as a common guiding principle in early animal development","_id":"917c023a-16d5-11f0-9cad-eb5cafc52090"}],"doi_confirm":"1","OA_place":"publisher","status":"public","date_created":"2026-09-04T11:54:20Z"}]