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Peer-reviewedCC BY 4.0The EMBO Journal

Mechanical constraints regulate embryonic stem cell mitosis in the developing brain

  • Véronique Marthiens
  • Lin Jawish
  • Margaux Malosse
  • Clara Basto
  • Denis Krndija
  • Anne-Sophie Macé
  • Elmar Laigna
  • Antonia Terrizzano
  • Corentin Peyret
  • Teng Pan
  • Olivier Zajac
  • Louisiane Perrin
3 more authors
  • Elsa Logarinho
  • Catherine Villard
  • Renata Basto
Open at sourcePDFDOICite

Abstract

Research on mitosis has predominantly examined cell-autonomous mechanisms, yet its regulation and consequences within the broader physiological context remain largely unexplored. It remains, therefore, unknown whether and how spindle assembly and chromosome segregation are influenced by tissue properties. We have investigated this question in the mammalian embryonic brain, using high-resolution microscopy combined with pharmacological perturbations and minimal cell systems to break down the contribution of tissue environment to mitotic fidelity. We found that cell density imposes biomechanical constraints upon the apical radial glial (aRG) cell population during their highly proliferative period, which enhances spindle pole microtubule polymerization rates and potentiates chromosome missegregation. Mechanistically, we show that cortical tension relying on branched actin organization at the cell cortex conveys mechanical stress exerted by cell density. We identified the microtubule depolymerase MCAK/Kif2C as a critical effector downstream of cortical actin, linking actin dynamics to spindle pole activity. Altogether, our findings demonstrate that aRG are mechanosensitive during their expansion phase, and that excessive biomechanical stress, imposed by high cell density in developing tissues, can disrupt mitotic fidelity.

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Cite

BibTeXRIS
BibTeX
@article{marthiens2026mechanical,
  title = {{Mechanical constraints regulate embryonic stem cell mitosis in the developing brain}},
  author = {Véronique Marthiens and Lin Jawish and Margaux Malosse and Clara Basto and Denis Krndija and Anne-Sophie Macé and Elmar Laigna and Antonia Terrizzano and Corentin Peyret and Teng Pan and Olivier Zajac and Louisiane Perrin and Elsa Logarinho and Catherine Villard and Renata Basto},
  journal = {The EMBO Journal},
  year = {2026},
  month = jul,
  doi = {10.1038/s44318-026-00848-3},
  url = {https://hal.science/hal-05765666v1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Mechanical constraints regulate embryonic stem cell mitosis in the developing brain
AU  - Véronique Marthiens
AU  - Lin Jawish
AU  - Margaux Malosse
AU  - Clara Basto
AU  - Denis Krndija
AU  - Anne-Sophie Macé
AU  - Elmar Laigna
AU  - Antonia Terrizzano
AU  - Corentin Peyret
AU  - Teng Pan
AU  - Olivier Zajac
AU  - Louisiane Perrin
AU  - Elsa Logarinho
AU  - Catherine Villard
AU  - Renata Basto
PY  - 2026
DA  - 2026/07/10
JO  - The EMBO Journal
DO  - 10.1038/s44318-026-00848-3
UR  - https://hal.science/hal-05765666v1
AB  - Research on mitosis has predominantly examined cell-autonomous mechanisms, yet its regulation and consequences within the broader physiological context remain largely unexplored. It remains, therefore, unknown whether and how spindle assembly and chromosome segregation are influenced by tissue properties. We have investigated this question in the mammalian embryonic brain, using high-resolution microscopy combined with pharmacological perturbations and minimal cell systems to break down the contribution of tissue environment to mitotic fidelity. We found that cell density imposes biomechanical constraints upon the apical radial glial (aRG) cell population during their highly proliferative period, which enhances spindle pole microtubule polymerization rates and potentiates chromosome missegregation. Mechanistically, we show that cortical tension relying on branched actin organization at the cell cortex conveys mechanical stress exerted by cell density. We identified the microtubule depolymerase MCAK/Kif2C as a critical effector downstream of cortical actin, linking actin dynamics to spindle pole activity. Altogether, our findings demonstrate that aRG are mechanosensitive during their expansion phase, and that excessive biomechanical stress, imposed by high cell density in developing tissues, can disrupt mitotic fidelity.
SN  - 0261-4189
SN  - 1460-2075
ER  -