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

PLoS One. 2016 Mar 9;11(3):e0151251. doi: 10.1371/journal.pone.0151251. eCollection 2016.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corneal Dystrophies, Hereditary / metabolism
  • Disease Models, Animal
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Endothelium, Corneal / metabolism
  • Female
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mammals
  • Mice
  • Mice, Mutant Strains
  • Polyploidy
  • Protein-Serine-Threonine Kinases / metabolism*
  • Transcription Factor AP-1 / metabolism

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Transcription Factor AP-1
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila
  • JNK Mitogen-Activated Protein Kinases