Polyploidy (the more than doubling of a cell’s genome) frequently arises during organogenesis, tissue repair, and age-associated diseases. Despite its prevalence, major gaps exist in how polyploid cells emerge and affect tissue function. Studies have begun to elucidate the signals required for polyploid cell growth as well as the advantages and disadvantages of polyploidy in health and disease. This review highlights the recent advances on the role and regulation of polyploidy in Drosophila and vertebrate models. The newly discovered versatility of polyploid cells has the potential to provide alternative strategies to promote tissue growth and repair, while limiting disease and dysfunction.
Polyploidy is a frequent phenomenon whose impact on organismal health and disease is still poorly understood. A cell is defined as polyploid if it contains more than the diploid copy of its chromosomes, which is a result of endoreplication or cell fusion. In tissue repair, wound-induced polyploidization (WIP) has been found to be a conserved healing strategy from fruit flies to vertebrates. WIP has several advantages over cell proliferation, including resistance to oncogenic growth and genotoxic stress. The challenge has been to identify why polyploid cells arise and how these unique cells function. Provided is a detailed protocol to study WIP in the adult fruit fly epithelium where polyploid cells are generated within 2 days after a puncture wound. Taking advantage of D. melanogaster's extensive genetic tool kit, the genes required to initiate and regulate WIP, including Myc, have begun to be identified. Continued studies using this method can reveal how other genetic and physiological variables including sex, diet, and age regulate and influence WIP's function.. This method increases the suitability of the adult D. melanogaster abdominal epithelium as a model to study the role and regulation of polyploidy in wound repair.
A key step in tissue repair is to replace lost or damaged cells. This occurs via two strategies: restoring cell number through proliferation or increasing cell size through polyploidization. Studies in Drosophila and vertebrates have demonstrated that polyploid cells arise in adult tissues, at least in part, to promote tissue repair and restore tissue mass. However, the signals that cause polyploid cells to form in response to injury remain poorly understood. In the adult Drosophila epithelium, wound-induced polyploid cells are generated by both cell fusion and endoreplication, resulting in a giant polyploid syncytium. Here, we identify the integrin focal adhesion complex as an activator of wound-induced polyploidization. Both integrin and focal adhesion kinase are upregulated in the wound-induced polyploid cells and are required for Yorkie-induced endoreplication and cell fusion. As a result, wound healing is perturbed when focal adhesion genes are knocked down. These findings show that conserved focal adhesion signaling is required to initiate wound-induced polyploid cell growth.
Polyploidy is a frequent phenomenon whose impact on organismal health and disease is still poorly understood. A cell is defined as polyploid if it contains more than the diploid copy of its chromosomes, which is a result of endoreplication or cell fusion. In tissue repair, wound-induced polyploidization (WIP) has been found to be a conserved healing strategy from fruit flies to vertebrates. WIP has several advantages over cell proliferation, including resistance to oncogenic growth and genotoxic stress. The challenge has been to identify why polyploid cells arise and how these unique cells function. Provided is a detailed protocol to study WIP in the adult fruit fly epithelium where polyploid cells are generated within 2 days after a puncture wound. Taking advantage of D. melanogaster's extensive genetic tool kit, the genes required to initiate and regulate WIP, including Myc, have begun to be identified. Continued studies using this method can reveal how other genetic and physiological variables including sex, diet, and age regulate and influence WIP's function. 1,2. Postembryonic wound healing in larvae, pupae, and adult fruit flies results in extracellular matrix remodeling, melanin scar formation, and epithelial cell growth 3,4,5,6. The epithelial cells increase in size by cell fusion and the endocycle, an incomplete cell cycle that bypasses mitosis 3,4,7,8. As result, cell loss is compensated by polyploid cell growth instead of cell division. The adult fly hindgut, midgut, and follicular epithelium also rely on polyploid cell growth to compensate for cell loss after tissue damage 9,10,11 .Polyploidy is a well-known aspect of organismal development in plants and insects, but in the last few years it has become more apparent that polyploidy is a conserved tissue repair strategy in vertebrates 12 . The zebrafish, which has the capacity to regenerate its heart, relies on polyploid cell growth to heal damaged epicardium 13 . Polyploidy also contributes to mammalian liver regeneration and kidney tubule epithelium repair after acute injury 14,15 . In these examples, polyploid cells are generated by endoreplication via either endocycle or endomitosis, which results in a binucleated cell due to a block in cytokinesis 12 . The enigma is why polyploid cells arise during wound repair and how polyploidy affects tissue function. Recent studies have provided new insight into the question of whether polyploidy offers a healing advantage or disadvantage. In zebrafish epicardium, polyploidy enhanced the speed of wound healing
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