Wound-induced polyploidization is dependent on integrin-yki signaling

Abstract

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.

The endocycle restores tissue tension in the Drosophila abdomen post wound repair

“…In Drosophila , increased mechanical tension was also shown to regulate cell-to-cell fusion during muscle development ( Kim et al, 2015 ). We recently showed that wound-induced polyploidization (WIP) in adult fly epithelium relies on integrin and focal adhesion kinase ( Besen-McNally et al, 2021 ). Other biophysical forces, including shear stress, are required to induce polyploidization of megakaryocytes during maturation ( Jiang et al, 2014 ).…”

Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

“…This phenomenon was described in cardiomyocytes from the hypoplastic left ventricle in the human and neonatal mice [ 94 , 102 ]. It was also observed in cardiomyocytes and hepatocytes of neonatal rats that survived severe inflammatory stress [ 7 , 9 , 75 ], and in drosophila epithelial cells involved in wound healing [ 1 , 103 ]. Thus, evidence coming from various objects and fields of research suggest that polyploidy is a way of adaptation to stress and related complications like increased ROS production and DNA instability.…”

Integrins in the Immunity of Insects: A Review

“…However, the signaling required for polyploid cells in response to injury in insects has recently been discovered by Besen-McNally et al. ( 101 ). The authors demonstrated that wound-induced polyploid cells are generated by cell fusion and endoreplication, resulting in a giant polyploid syncytium in the adult Drosophila epithelium.…”

“…They further showed that the integrin focal adhesion complex is 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 evidenced by wound healing is perturbed when focal adhesion genes (Mys and Fak) are knocked down ( 101 ). However, the focal adhesion complex that regulates cell fusion and formation of syncytium other signaling mechanisms may also derive wound closure in insects that may also be connected with integrin proteins that are still unidentified.…”