Liver tetraploidization is controlled by a new process of incomplete cytokinesis
Abstract
Cytokinesis is precisely controlled in both time and space to ensure equal distribution of the genetic material between daughter cells. Incomplete cytokinesis can be associated with developmental or pathological cell division programs leading to tetraploid progenies. In this study we decipher a new mechanism of incomplete cytokinesis taking place in hepatocytes during post-natal liver growth. This process is initiated in vivo after weaning and is associated with an absence of anaphase cell elongation. In this process, formation of a functional contractile actomyosin ring was never observed; indeed, actin filaments spread out along the cortex were not concentrated to the putative site of furrowing. Recruitment of myosin II to the cortex, controlled by Rho-kinase, was impaired. Astral microtubules failed to contact the equatorial cortex and to deliver their molecular signal, preventing activation of the RhoA pathway. These findings reveal a new developmental cell division program in the liver that prevents cleavage-plane specification.
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Between P14 and P21, a specialized mitotic program involving programmed cytokinesis failure promotes rapid binucleation and polyploidization of hepatocytes.
“However, between P14 and P21, a specialized mitotic program involving programmed cytokinesis failure promotes rapid binucleation and polyploidization of hepatocytes (Margall-Ducos et al. 2007; Gentric and Desdouets 2014; Hsu et al. 2016).”
From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Margall-Ducos et al. 2007
The suckling-to-weaning transition period (P14-P21 in rodents) is particularly significant for liver maturation, as hepatocyte size, ploidy, and metabolism increase markedly during this time frame.
“The suckling-to-weaning transition period (P14–P21 in rodents) is particularly significant for liver maturation, as hepatocyte size, ploidy, and metabolism increase markedly during this time frame (Margall-Ducos et al. 2007).”
From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Margall-Ducos et al. 2007
Mechanisms regulating hepatocyte ploidy include insulin signalling through the P13K-AKT pathway, which is influenced by weaning and induces formation of binucleate tetraploid hepatocytes during postnatal liver growth.
“Mechanisms regulating hepatocyte ploidy include insulin signalling through the P13K-AKT pathway, which is influenced by weaning67 and induces formation of binucleate tetraploid hepatocytes during postnatal liver growth.68,69”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [67]
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References 42 · Cited by 170
- Authors
- Margall-Ducos, G., Celton-Morizur, S., Couton, D., Brégerie, O., & Desdouets, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France
- Inserm, U785, Université Paris sud, Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif F-94804, France
- Corresponding author
- Desdouets, Chantal
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2007-10-15
- Volume
- 120
- Issue
- 20
- Pages
- 3633-3639
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2023204965
- Cited by
- 170
- References
- 42
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 12 · 2023: 8 · 2022: 8 · 2021: 17 · 2020: 14 · 2019: 10 · 2018: 10 · 2017: 14 · 2016: 4 · 2015: 8 · 2014: 3 · 2013: 9 · 2012: 17
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- incomplete cytokinesis, hepatocytes, myosin II, Rho kinase, RhoA signaling, astral microtubules, actomyosin ring, cell division
- MeSH terms
- Actins, Anaphase, Animals, Cell Cycle, Cells, Cultured, Cytoskeleton, Liver, Male, Actin Cytoskeleton, Microtubule-Associated Proteins, Microtubules, Spindle Apparatus, Polyploidy, Rats, Wistar, rhoA GTP-Binding Protein, Hepatocytes, Myosin Type II, Cell Shape, Cytokinesis, Rats
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