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

Document Type

Article

Publication Date

10-15-2023

Keywords

Animals, Mice, Drosophila, alpha Catenin, Cell Fusion, Drosophila Proteins, Polyploidy

JAX Source

J Cell Sci. 2023;136(20):jcs260974

ISSN

1477-9137

PMID

37732459

DOI

https://doi.org/10.1242/jcs.260974

Grant

This work was supported by MDI Biological Laboratory, Procter Award to V.P.L., Boston College, and the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35GM124691 to V.P.L. and the National Eye Institute under EY027860 and EY011996 to P.M.N. Deposited in PMC for release after 12 months.

Abstract

A characteristic of normal aging and age-related diseases is the remodeling of the cellular organization of a tissue through polyploid cell growth. Polyploidy arises from an increase in nuclear ploidy or the number of nuclei per cell. However, it is not known whether age-induced polyploidy is an adaption to stressors or a precursor to degeneration. Here, we find that abdominal epithelium of the adult fruit fly becomes polyploid with age through generation of multinucleated cells by cell fusion. Inhibition of fusion does not improve the lifespan of the fly, but does enhance its biomechanical fitness, a measure of the healthspan of the animal. Remarkably, Drosophila can maintain their epithelial tension and abdominal movements with age when cell fusion is inhibited. Epithelial cell fusion also appears to be dependent on a mechanical cue, as knockdown of Rho kinase, E-cadherin or α-catenin is sufficient to induce multinucleation in young animals. Interestingly, mutations in α-catenin in mice result in retina pigment epithelial multinucleation associated with macular disease. Therefore, we have discovered that polyploid cells arise by cell fusion and contribute to the decline in the biomechanical fitness of the animal with age.

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