Epithelial mechanics are maintained by inhibiting cell fusion with age in <i>Drosophila</i>

Dehn, Ari S.; Duhaime, Levi; Gogna, Navdeep; Nishina, Patsy M.; Kelley, Kristina; Losick, Vicki P.

doi:10.1242/jcs.260974

Cited by 5 publications

(2 citation statements)

References 50 publications

(86 reference statements)

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“…By fusing, cells reduce the need for adhesion remodeling and intercalation as the leading edge becomes smaller. Moreover, the resulting larger cell has significantly more fluidity and less epithelial tension than the diploid progenitors, as recently demonstrated in syncytia formed by age-induced epidermal cell fusion [28].…”

Section: Discussionmentioning

confidence: 94%

Wound-Induced Syncytia Outpace Mononucleate Neighbors duringDrosophilaWound Repair

White

Ruark

et al. 2023

Preprint

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Injury is a constant reality of life, and survival requires all organisms to repair wounds. Cell behaviors like proliferation, migration, and invasion replace missing cells and close wounds. However, the contribution of other wound-induced cell behaviors is not understood, including formation of multi-nucleate syncytia. Wound-induced epithelial syncytia were first reported around epidermal puncture wounds in Drosophila larvae and adults with similarities to multinucleation increases in mammalian cardiomyocytes after pressure overload. Although these tissues are post-mitotic, syncytia have more recently been reported in mitotically competent tissues: around laser wounds in Drosophila pupal epidermis and in zebrafish epicardium damaged by endotoxin, microdissection, or laser. Further, injury induces fusion of other cells: after injury, bone marrow derived cells fuse with various somatic cells to promote repair, and after biomaterial implantation, immune cells fuse into multinucleated giant cells associated with rejection . These observations raise the possibility that syncytia offer adaptive benefits, but it is unknown what those benefits are. Here, we utilize in vivo live imaging to analyze wound-induced syncytia in mitotically competent Drosophila pupae. Almost half the epithelial cells near a wound fuse, forming large syncytia. Syncytia migrate rapidly, outpacing diploid cells to complete wound closure. We show syncytia can both pool resources of their component cells to concentrate them toward the wound, and reduce cell intercalation during wound closure, two mechanisms for speeding wound repair. In addition to wound healing, these properties of syncytia are likely to contribute to their roles in development and pathology.

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Section: Discussionmentioning

confidence: 94%

Wound-Induced Syncytia Outpace Mononucleate Neighbors duringDrosophilaWound Repair

White

Ruark

et al. 2023

Preprint

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“…syncytia with large nuclei in Drosophila's abdominal epithelium [67,68]. This age-induced hyperpolyploidy was found to be suppressible by inhibiting cell fusion.…”

Section: Dehn Et Al Observed High-grade Age-induced Polyploidy Occurr...mentioning

confidence: 96%

The enigma of cancer polyploidy as deciphered by evolutionary cancer stem cell biology (ECCB)

Niculescu,

Niculescu

2024

Academia Medicine

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Cell cycle re-entry in the agingDrosophilabrain

Damschroder,

Sun,

McDonald

et al. 2024

Preprint

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The brain is an organ comprised mostly of long-lived, quiescent cells that perform vital functions throughout an animal’s life. Due to the brain’s limited regenerative ability, these long-lived cells must engage unique mechanisms to cope with accumulated damage over time. We have shown that a subset of differentiated neuronal and glial cells in the fruit fly brain become polyploid during adulthood. Cell cycle re-entry in the brain has previously been associated with neurodegeneration, but there may be a more complex relationship between polyploidy and cell fitness in the brain. Here, we examine how known lifespan modifiers influence the accumulation of polyploidy in the aging fly brain. Flies aged at a low temperature, or with a low protein diet, accumulate polyploid cells in the brain more slowly than expected if this phenotype were solely regulated by lifespan mechanisms. Despite the slower accumulation of polyploid cells, animals under conditions that extend lifespan eventually reach similar levels of polyploidy in the brain as controls. Our work suggests known lifespan modifiers can influence the timing of cell cycle re-entry in the adult brain, indicating there is a flexible window of cell cycle plasticity in the aging brain.

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Epithelial mechanics are maintained by inhibiting cell fusion with age in Drosophila

Cited by 5 publications

References 50 publications

Wound-Induced Syncytia Outpace Mononucleate Neighbors duringDrosophilaWound Repair

Wound-Induced Syncytia Outpace Mononucleate Neighbors duringDrosophilaWound Repair

The enigma of cancer polyploidy as deciphered by evolutionary cancer stem cell biology (ECCB)

Cell cycle re-entry in the agingDrosophilabrain

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