Decrease in Cell Volume Generates Contractile Forces Driving Dorsal Closure

Abstract

Biological tissues must generate forces to shape organs and achieve proper development. Such forces often result from the contraction of an apical acto-myosin meshwork. Here we describe an alternative mechanism for tissue contraction, based on individual cell volume change. We show that during Drosophila dorsal closure (DC), a wound healing-related process, the contraction of the amnioserosa (AS) is associated with a major reduction of the volume of its cells, triggered by caspase activation at the onset of the apoptotic program of AS cells. Cell volume decrease results in a contractile force that promotes tissue shrinkage. Estimating mechanical tensions with laser dissection and using 3D biophysical modeling, we show that the cell volume decrease acts together with the contraction of the actin cable surrounding the tissue to govern DC kinetics. Our study identifies a mechanism by which tissues generate forces and movements by modulating individual cell volume during development.

Cell type-specific adaptation of cellular and nuclear volume in micro-engineered 3D environments

“…In general, the cell volumes we obtained in our study were in the range of volumes measured for various cells in 2D studies (e.g., osteosarcoma cells: 1900 µm 3 [68]; human osteoblasts: ~5000 µm 3 [68]; human dermal fibroblast: 2400 µm 3 [69]; rapidly proliferating mesenchymal stem cells: 1200-2100 µm 3 [68]) and for further cell types [61,[68][69][70][71]. However, so far only few studies have analyzed single cell volumes in artificial 3D environments [72,73]. for fibroblasts cultured in 3D scaffolds for 22 hours and observed that our 3D scaffolds are suitable for longer cell culture times.…”

Myosin II is not required forDrosophilatracheal branch elongation and cell intercalation

“…Furthermore, mutations often affect multiple cellular processes and therefore are prone to generate indirect effects or lead to adaptation. To overcome these drawbacks, time-and tissue-specific expression of dominant-negative forms of MyoII or upstream regulators have often been used (Fischer et al, 2014;Franke et al, 2010;Saias et al, 2015). However, these tools seemed to be less efficient in their depleting competence and gave rise to much milder phenotypes than the ones observed with deGradFP (see also Pasakarnis et al, 2016 and Table S1).…”

Actin Rings of Power

“…A contractile supracellular actomyosin cable positioned at the leading edge of the surrounding epithelium has been suggested to act as a purse-string driving dorsal closure (Hutson et Young et al, 1993). In addition, the AS cells undergo pulsatile apical constrictions (Franke et al, 2005;Solon et al, 2009) and reduce their volume (Saias et al, 2015), and a fraction of these cells also delaminate , thereby contributing to dorsal closure by pulling on the margin of the surrounding epithelium. At the final stage of dorsal closure, actin-and microtubule-rich filopodia extend from the leading edge of epithelium toward the opposing epithelial edge, thereby zipping the two sheets of cells together (Jacinto et al, 2000;Jankovics and Brunner, 2006).…”

“…Initial laser ablation studies identified the multicellular purse-string within the leading-edge cells and the dynamic AS cells as the main motor driving dorsal closure (Hutson et al, 2003;Kiehart et al, 2000). Interestingly, a recent study revealed that the actomyosin cable in combination with AS cells, undergoing cell volume decrease, can trigger a force imbalance that is required to initiate and propagate the closure process (Saias et al, 2015).…”