Occluding junctions as novel regulators of tissue mechanics during wound repair

Abstract

In epithelial tissues, cells tightly connect to each other through cell-cell junctions, but they also present the remarkable capacity of reorganizing themselves without compromising tissue integrity. Upon injury, simple epithelia efficiently resolve small lesions through the action of actin cytoskeleton contractile structures at the wound edge and cellular rearrangements. However, the underlying mechanisms and how they cooperate are still poorly understood. In this study, we combine live imaging and theoretical modeling to reveal a novel and indispensable role for occluding junctions (OJs) in this process. We demonstrate that OJ loss of function leads to defects in wound-closure dynamics: instead of contracting, wounds dramatically increase their area. OJ mutants exhibit phenotypes in cell shape, cellular rearrangements, and mechanical properties as well as in actin cytoskeleton dynamics at the wound edge. We propose that OJs are essential for wound closure by impacting on epithelial mechanics at the tissue level, which in turn is crucial for correct regulation of the cellular events occurring at the wound edge.

The occluding junction protein Neurexin-IV is required for tissue integrity in the Drosophila wing disc epithelium

“…Finally, SJs regulate the mechanical properties of the embryonic epidermis [8]. On the other hand, we show that Nrx-IV loss of function does not seem to affect AJ localization, which is also supported by previous studies [16] [17] [18] [8].…”

“…Namely, it has been shown that Nrx-IV, together with other SJ molecules (Yurt, Coracle, and the Na + /K + -ATPase), acts to maintain apical-basal polarity during early embryonic stages, before the SJ barrier function is established, but not during late embryogenesis, when the SJ barrier function is fully established [14]. Other SJ proteins have also been shown to regulate cell shape and rearrangements during salivary gland formation and wound closure [15] [8].…”

“…Although the paracellular barrier is the most studied function of SJs, recent studies suggest they also play a role in epithelial morphogenesis independently of their barrier function [6] [7] [8]. For example, impairing SJ function during embryonic development leads to defects in diverse processes such as epithelial tube size, extracellular matrix deposition and cellular rearragements.…”

Drp1-mediated mitochondrial fission regulates calcium and F-actin dynamics during wound healing

“…Live imaging was performed as described previously (Carvalho et al, 2018). Dechorionated stage 15 embryos were mounted on their ventral side on glass-bottomed culture dishes (MatTek) with embryo glue (double-sided tape diluted in heptane) and covered with halocarbon oil 27 (Sigma-Aldrich).…”

“…Wound healing in simple epithelia is characterized by the accumulation of F-actin and Non-muscle Myosin II (Myosin) at the cell boundaries that face the wound, forming an actomyosin cable that contracts and brings cells together, thereby closing the wound (Bement et al, 1999; Danjo and Gipson, 1998; Kiehart et al, 2000; Xu and Chisholm, 2011). Additionally, wound healing involves cell crawling mediated by actin protrusions (Abreu-Blanco et al, 2012; Verboon and Parkhurst, 2015) and cellular rearrangements (Carvalho et al, 2018; Razzell et al, 2014).…”