Wound-Induced Polyploidization: Regulation by Hippo and JNK Signaling and Conservation in Mammals

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 (W...

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Bibliographic Details
Published in:PloS one 2016-03, Vol.11 (3), p.e0151251-e0151251
Main Authors: Losick, Vicki P, Jun, Albert S, Spradling, Allan C
Format: Article
Language:English
Subjects:
Abdomen
Analysis
Animals
Automation
Biology and Life Sciences
Cardiomyocytes
Cell cycle
Cell death
Cell division
Cell growth
Cell proliferation
Cellular signal transduction
Conservation
Cornea
Corneal Dystrophies, Hereditary - metabolism
Corneal dystrophy
Deoxyribonucleic acid
Disease Models, Animal
DNA
Drosophila
Drosophila Proteins - metabolism
Dystrophy
Embryology
Endothelium
Endothelium, Corneal - metabolism
Epidermis
Female
Genomes
Homeostasis
Insects
Intracellular Signaling Peptides and Proteins - metabolism
JNK Mitogen-Activated Protein Kinases - metabolism
JNK protein
Kinases
Liver diseases
Mammals
Medicine and Health Sciences
Mice
Mice, Mutant Strains
Physiological aspects
Polyploidy
Protein-Serine-Threonine Kinases - metabolism
Research and Analysis Methods
Signaling
Stem cell transplantation
Stem cells
Tissues
Transcription Factor AP-1 - metabolism
Transcription factors
Wound care
Wounds
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0151251