---
OA_place: repository
OA_type: green
_id: '18446'
abstract:
- lang: eng
  text: How living systems achieve precision in form and function despite their intrinsic
    stochasticity is a fundamental yet ongoing question in biology. We generated morphomaps
    of preimplantation embryogenesis in mouse, rabbit, and monkey embryos, and these
    morphomaps revealed that although blastomere divisions desynchronized passively,
    8-cell embryos converged toward robust three-dimensional shapes. Using topological
    analysis and genetic perturbations, we found that embryos progressively changed
    their cellular connectivity to a preferred topology, which could be predicted
    by a physical model in which actomyosin contractility and noise facilitate topological
    transitions, lowering surface energy. This mechanism favored regular embryo packing
    and promoted a higher number of inner cells in the 16-cell embryo. Synchronized
    division reduced embryo packing and generated substantially more misallocated
    cells and fewer inner-cell–mass cells. These findings suggest that stochasticity
    in division timing contributes to robust patterning.
acknowledgement: "We are grateful to the members of the Hiiragi laboratory for discussions
  and comments on the manuscript: R. Bloehs, S. Friese, S. Hozeifi, L. Pérez, and
  W. Schwarzer for their technical support; V. Janssen for establishing the PAB protocol;
  members of the Tsukiyama group for the animal care with monkeys, in particular H.
  Tsuchiya and M. Nakaya; Unité Commune d’Expérimentation Animale (UCEA, Jouy-en-Josas,
  France) for the animal care with rabbits; the EMBL electronic and mechanical workshops
  and the EMBL animal facility for their support; We thank Luxendo for the close collaboration
  in developing the light-sheet microscopy for mammalian embryos.\r\nFunding: This
  work was funded by the following: EMBL Interdisciplinary Postdoc Program (EIPOD)
  under Marie Sklodowska Curie Actions COFUND III RTD (to D.F.); JSPS Overseas Research
  Fellowship (to T.I.); Field of excellence “Complexity of life in basic research
  and innovation” of the University of Graz (to B.C.M.); European Research Council,
  ERC Advanced Grant “SelforganisingEmbryo”, grant agreement 742732; ERC Advanced
  Grant “COORDINATION” grant agreement 101055287 (to T.H.); Stichting LSH-TKI, grant
  LSHM21020 (to T.H.) JSPS KAKENHI grants JP21H05038 and JP22H05166 (to T.H.)"
article_number: eadh1145
article_processing_charge: No
article_type: original
author:
- first_name: Dimitri
  full_name: Fabrèges, Dimitri
  last_name: Fabrèges
- first_name: Bernat
  full_name: Corominas-Murtra, Bernat
  id: 43BE2298-F248-11E8-B48F-1D18A9856A87
  last_name: Corominas-Murtra
  orcid: 0000-0001-9806-5643
- first_name: Prachiti
  full_name: Moghe, Prachiti
  last_name: Moghe
- first_name: Alison
  full_name: Kickuth, Alison
  last_name: Kickuth
- first_name: Takafumi
  full_name: Ichikawa, Takafumi
  last_name: Ichikawa
- first_name: Chizuru
  full_name: Iwatani, Chizuru
  last_name: Iwatani
- first_name: Tomoyuki
  full_name: Tsukiyama, Tomoyuki
  last_name: Tsukiyama
- first_name: Nathalie
  full_name: Daniel, Nathalie
  last_name: Daniel
- first_name: Julie
  full_name: Gering, Julie
  last_name: Gering
- first_name: Anniek
  full_name: Stokkermans, Anniek
  last_name: Stokkermans
- first_name: Adrian
  full_name: Wolny, Adrian
  last_name: Wolny
- first_name: Anna
  full_name: Kreshuk, Anna
  last_name: Kreshuk
- first_name: Véronique
  full_name: Duranthon, Véronique
  last_name: Duranthon
- first_name: Virginie
  full_name: Uhlman, Virginie
  last_name: Uhlman
- 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: Takashi
  full_name: Hiiragi, Takashi
  last_name: Hiiragi
citation:
  ama: Fabrèges D, Corominas-Murtra B, Moghe P, et al. Temporal variability and cell
    mechanics control robustness in mammalian embryogenesis. <i>Science</i>. 2024;386(6718).
    doi:<a href="https://doi.org/10.1126/science.adh1145">10.1126/science.adh1145</a>
  apa: Fabrèges, D., Corominas-Murtra, B., Moghe, P., Kickuth, A., Ichikawa, T., Iwatani,
    C., … Hiiragi, T. (2024). Temporal variability and cell mechanics control robustness
    in mammalian embryogenesis. <i>Science</i>. AAAS. <a href="https://doi.org/10.1126/science.adh1145">https://doi.org/10.1126/science.adh1145</a>
  chicago: Fabrèges, Dimitri, Bernat Corominas-Murtra, Prachiti Moghe, Alison Kickuth,
    Takafumi Ichikawa, Chizuru Iwatani, Tomoyuki Tsukiyama, et al. “Temporal Variability
    and Cell Mechanics Control Robustness in Mammalian Embryogenesis.” <i>Science</i>.
    AAAS, 2024. <a href="https://doi.org/10.1126/science.adh1145">https://doi.org/10.1126/science.adh1145</a>.
  ieee: D. Fabrèges <i>et al.</i>, “Temporal variability and cell mechanics control
    robustness in mammalian embryogenesis,” <i>Science</i>, vol. 386, no. 6718. AAAS,
    2024.
  ista: Fabrèges D, Corominas-Murtra B, Moghe P, Kickuth A, Ichikawa T, Iwatani C,
    Tsukiyama T, Daniel N, Gering J, Stokkermans A, Wolny A, Kreshuk A, Duranthon
    V, Uhlman V, Hannezo EB, Hiiragi T. 2024. Temporal variability and cell mechanics
    control robustness in mammalian embryogenesis. Science. 386(6718), eadh1145.
  mla: Fabrèges, Dimitri, et al. “Temporal Variability and Cell Mechanics Control
    Robustness in Mammalian Embryogenesis.” <i>Science</i>, vol. 386, no. 6718, eadh1145,
    AAAS, 2024, doi:<a href="https://doi.org/10.1126/science.adh1145">10.1126/science.adh1145</a>.
  short: D. Fabrèges, B. Corominas-Murtra, P. Moghe, A. Kickuth, T. Ichikawa, C. Iwatani,
    T. Tsukiyama, N. Daniel, J. Gering, A. Stokkermans, A. Wolny, A. Kreshuk, V. Duranthon,
    V. Uhlman, E.B. Hannezo, T. Hiiragi, Science 386 (2024).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: "All original code and data reported in this paper is publicly
  available as of the date of publication on Zenodo (124).\r\n124\r\nD. Fabrèges,
  B. Corominas-Murtra, P. Moghe, A. Kickuth, T. Ichikawa, C. Iwatani, T. Tsukiyama,
  N. Daniel, J. Gering, A. Stokkermans, A. Wolny, A. Kreshuk, V. Duranthon, V. Uhlmann,
  E. Hannezo, T. Hiiragi, Temporal variability and cell mechanics control robustness
  in mammalian embryogenesis, version 1.0, Zenodo (2024); https://doi.org/10.5281/ZENODO.12819781."
date_created: 2024-10-20T22:02:06Z
date_published: 2024-10-11T00:00:00Z
date_updated: 2026-10-01T10:54:32Z
day: '11'
department:
- _id: EdHa
doi: 10.1126/science.adh1145
external_id:
  isi:
  - '001422132300018'
  pmid:
  - '39388574'
fulldoi: https://doi.org/10.1126/science.adh1145
intvolume: '       386'
isi: 1
issue: '6718'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://hal.inrae.fr/hal-04447081v1/file/2023.01.24.525420.full.pdf
month: '10'
oa: 1
oa_version: Submitted Version
pmid: 1
publication: Science
publication_identifier:
  eissn:
  - 1095-9203
publication_status: published
publisher: AAAS
quality_controlled: '1'
related_material:
  record:
  - id: '23023'
    relation: research_data
    status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Temporal variability and cell mechanics control robustness in mammalian embryogenesis
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 386
year: '2024'
...