Abstract
Tissue integrity and homeostasis often rely on the proliferation of stem cells or differentiated cells to replace lost, aged, or damaged cells. Recently, we described an alternative source of cell replacement- the expansion of resident, non-dividing diploid cells by wound-induced polyploidization (WIP). Here we show that the magnitude of WIP is proportional to the extent of cell loss using a new semi-automated assay with single cell resolution. Hippo and JNK signaling regulate WIP; unexpectedly however, JNK signaling through AP-1 limits rather than stimulates the level of Yki activation and polyploidization in the Drosophila epidermis. We found that polyploidization also quantitatively compensates for cell loss in a mammalian tissue, mouse corneal endothelium, where increased cell death occurs with age in a mouse model of Fuchs Endothelial Corneal Dystrophy (FECD). Our results suggest that WIP is an evolutionarily conserved homeostatic mechanism that maintains the size and synthetic capacity of adult tissues.
Highlights
During the life of an organism physiological insults including injury, aging, and degenerative disease can damage tissues leading to the loss of mature cells
We find that the Drosophila epidermis tightly controls the spatial distribution, extent, and the magnitude of wound-induced polyploidization (WIP) such that the number of new genomes produced regionally closely matches the number of genomes lost to wounding
Individual fly epidermal nuclei expressing a nuclear GFP transgene driven by the epidermal-Gal4, which is specific to the adult epidermis and co-localizes with epidermal nuclear marker Grainy-head (Grh), were identified using Fiji software and their outlines recorded (Fig 1 and S1 Fig) [23]
Summary
During the life of an organism physiological insults including injury, aging, and degenerative disease can damage tissues leading to the loss of mature cells. A variety of mechanisms exist to compensate for cell loss and maintain adult tissue homeostasis [1,2,3,4,5]. Differentiated cells provide a second source of new cells in tissues such as liver, where they can be induced to divide and contribute to cell replacement [7]. Animals that can regenerate their limbs re-activate mature tissue cells to dedifferentiate to form the blastema and proliferate to compensate for cell loss [1, 8]. A third source of cell replacement termed wound-induced polyploidization (WIP) was described in the adult Drosophila epidermis and hindgut [4, 9]. Post-mitotic differentiated diploid cells in these tissues respond to wounding by re-entering the cell cycle, but rather than proliferating mitotically they enter the endocycle and polyploidize.
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