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Review
. 2016 Jun 1;5(6):271-278.
doi: 10.1089/wound.2014.0545.

Wound-Induced Polyploidy Is Required for Tissue Repair

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Free PMC article
Review

Wound-Induced Polyploidy Is Required for Tissue Repair

Vicki P Losick. Adv Wound Care (New Rochelle). .
Free PMC article

Abstract

Significance: All organs suffer wounds to some extent during an animal's lifetime and to compensate for cell loss, tissues often rely on cell division. However, many organs are made up of differentiated cells with only a limited capacity to divide. It is not well understood how cells are replaced in the absence of cell division. Recent Advances: Recent studies in the model organism Drosophila melanogaster have proven that wound-induced polyploidy (WIP) is an essential mechanism to replace tissue mass and restore tissue integrity in the absence of cell division. In this repair mechanism, preexisting differentiated cells increase their DNA content and cell size by becoming polyploid. Critical Issues: Cells within mammalian organs such as the liver, heart, and cornea have also been observed to increase their DNA ploidy in response to injury, suggesting that WIP may be an evolutionarily conserved mechanism to compensate for cell loss. Future Directions: The Hippo signal transduction pathway is required for differentiated cells to initiate WIP in Drosophila. Continued studies in Drosophila will help to identify other signaling pathways required for WIP as well as the conserved mechanisms that polyploid cells may play during wound repair in all organisms.

Figures

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Vicki P. Losick, PhD
<b>Figure 1.</b>
Figure 1.
Cellular mechanisms of polyploid cell generation. Cells with more than diploid genomic content 4C or greater are considered polyploid. There are multiple mechanisms cells use to become polyploid. A diploid cell (brown) can enter an endocycle (A), where a cell duplicates its genome to become a mononucleated polyploid cell by bypassing mitosis. Cells can also go through endomitosis (B) where M phase is truncated (M*). In this case, a cell does not complete cytokinesis resulting in a binucleated polyploid cell. (C) Cells can also fuse together generating one enlarged multinucleated cell. In these cases, DNA ploidy is linked to cell size with increases in one value typically associated with the proportional increase in the other. Successive events or combinations of these processes will result in even larger cells with higher ploidy values.
<b>Figure 2.</b>
Figure 2.
Wound-induced polyploidy is required to heal the adult fly epidermis. (A) An illustration of the adult Drosophila melanogaster abdomen and the area injured (boxed). (B) Immunofluorescent image of the ventral epidermis of the adult female fruit fly. The epidermis is organized into a monolayer of diploid cells organized into rows. For all images, epidermal nuclei are green and cell–cell FasIII septate junctions are in magenta. (C) Dramatic remodeling of the epidermis occurs after injury as a result of both the growth (via the endocycle) and fusion of the preexisting epidermal cells. As a consequence, a giant polyploid syncytium (outlined by the yellow dashed line) encompasses the area under the wound scab. Individual epidermal cells enlarge (arrowhead) and fuse into smaller syncytia (arrows) on the periphery. (D) Epidermal repair can be inhibited when polyploidy is blocked by perturbing both fusion and endoreplication simultaneously (reprinted by permission from Losick et al.).
<b>Figure 3.</b>
Figure 3.
Quiescent epidermal cells in adult fly epidermis endoreplicate in response to injury. In response to injury, quiescent epidermal cells surrounding a puncture wound enter S phase and become ready labeled with the S phase marker EdU at 2 days postinjury. These EdU+cells grow instead of dividing by entering the endocycle. Shown is an immunofluorescent image of the wound zone with EdU+cells in white. The wound site is outlined by the magenta dashed line.
<b>Figure 4.</b>
Figure 4.
The Hippo pathway regulates tissue repair by cell division or endoreplication. The Hippo signal transduction pathway regulates the cotranscriptional activator Yorkie (Yki) to control tissue repair by cell division or endoreplication depending on the cell's differentiated state. In stem cells, Yki induces expression of the S phase cyclin E stimulating cells to divide. In differentiated cell types, this same signaling pathway appears to induce endoreplication by stimulating cells to grow instead of dividing. This model suggests that there are intrinsic differences between an undifferentiated and differentiated cell that trigger different repair outcomes using the same core Hippo signaling components.

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