Spatial, temporal and molecular hierarchies in the link between death, delamination and dorsal closure

Abstract

SUMMARYDead cells in most epithelia are eliminated by cell extrusion. Here, we explore whether cell delamination in the amnioserosa, a seemingly stochastic event that results in the extrusion of a small fraction of cells and known to provide a force for dorsal closure, is contingent upon the receipt of an apoptotic signal. Through the analysis of mutant combinations and the profiling of apoptotic signals in situ, we establish spatial, temporal and molecular hierarchies in the link between death and delamination. We show that although an apoptotic signal is necessary and sufficient to provide cell-autonomous instructions for delamination, its induction during natural delamination occurs downstream of mitochondrial fragmentation. We further show that apoptotic regulators can influence both delamination and dorsal closure cell non-autonomously, presumably by influencing tissue mechanics. The spatial heterogeneities in delamination frequency and mitochondrial morphology suggest that mechanical stresses may underlie the activation of the apoptotic cascade through their influence on mitochondrial dynamics. Our results document for the first time the temporal propagation of an apoptotic signal in the context of cell behaviours that accomplish morphogenesis during development. They highlight the importance of mitochondrial dynamics and tissue mechanics in its regulation. Together, they provide novel insights into how apoptotic signals can be deployed to pattern tissues.

Integration of actomyosin contractility with cell-cell adhesion during dorsal closure

“…We noticed that the tears within the AS usually appear at sites of cell delamination. It is known that around 10% of AS cells are eliminated from the epithelium through a mechanism involving cytoskeletal rearrangements in the delaminating cell and also in its nearest neighbours (Meghana et al, 2011;Muliyil et al, 2011;Toyama et al, 2008). We observe that the number of cell delamination events in mbs 541 mutant embryos increases, but this is not due to an increase in cell density (Fig.…”

“…means does not cause a loss of integrity of the tissue (Muliyil et al, 2011;Muliyil and Narasimha, 2014;Toyama et al, 2008), suggesting that cell delamination events per se do not generate tears. Instead, our results suggest that an imbalance in contractility and/or adhesion could also contribute to trigger cell delaminations.…”

α-Catenin stabilises Cadherin–Catenin complexes and modulates actomyosin dynamics to allow pulsatile apical contraction

“…One of the processes contributing to dorsal closure is the apoptosismediated extrusion from the plane of the amnioserosa epithelium of ∼10% of cells (Kiehart et al, 2000), through a mechanism involving cytoskeletal rearrangements in the delaminating cell and also in its nearest neighbours (Meghana et al, 2011;Muliyil et al, 2011). It has been shown that increasing the number of cell delamination events hastens closure (Toyama et al, 2008).…”

Spreading the word: non-autonomous effects of apoptosis during development, regeneration and disease

“…Some insight into the possible mechanism by which apoptosis affects the progression of closure came from a later study that investigated the spatial, temporal and molecular hierarchies in the relationship between apoptosis and delamination (Muliyil et al, 2011). In this study, it was shown that the apoptotic signal is essential for driving cell delamination, both autonomously and non-autonomously.…”

“…In this study, it was shown that the apoptotic signal is essential for driving cell delamination, both autonomously and non-autonomously. Furthermore, it was also shown that apoptosis influences the rates of apical constriction, suggesting that apoptosis regulators might regulate cell mechanics by inducing reorganization of the cytoskeleton (Muliyil et al, 2011).…”