---
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.
    <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>
  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>
  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>.
  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.
  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.” <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>.
  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
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  date_created: 2026-01-21T08:21:11Z
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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:
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  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
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type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 22
year: '2026'
...