Planar polarized actomyosin contractile flows control epithelial junction remodelling

Abstract

Force generation by Myosin-II motors on actin filaments drives cell and tissue morphogenesis. In epithelia, contractile forces are resisted at apical junctions by adhesive forces dependent on E-cadherin, which also transmits tension. During Drosophila embryonic germband extension, tissue elongation is driven by cell intercalation, which requires an irreversible and planar polarized remodelling of epithelial cell junctions. We investigate how cell deformations emerge from the interplay between force generation and cortical force transmission during this remodelling in Drosophila melanogaster. The shrinkage of dorsal-ventral-oriented ('vertical') junctions during this process is known to require planar polarized junctional contractility by Myosin II (refs 4, 5, 7, 12). Here we show that this shrinkage is not produced by junctional Myosin II itself, but by the polarized flow of medial actomyosin pulses towards 'vertical' junctions. This anisotropic flow is oriented by the planar polarized distribution of E-cadherin complexes, in that medial Myosin II flows towards 'vertical' junctions, which have relatively less E-cadherin than transverse junctions. Our evidence suggests that the medial flow pattern reflects equilibrium properties of force transmission and coupling to E-cadherin by α-Catenin. Thus, epithelial morphogenesis is not properly reflected by Myosin II steady state distribution but by polarized contractile actomyosin flows that emerge from interactions between E-cadherin and actomyosin networks.

Direct laser manipulation reveals the mechanics of cell contacts in vivo

“…At a one-cell distance (∼7 μm), we measured a time delay of 150 ± 85 ms (95% confidence interval), which corresponds to a propagation speed with a typical phase velocity of 45 μm·s −1 . This speed is much larger than the speed of actomyosin flows, which are observed in different systems, including Drosophila and C. elegans (0.1 μm·s −1 ) (21,29).…”

An Autoinhibited Structure of α-Catenin and Its Implications for Vinculin Recruitment to Adherens Junctions

“…As the activated pool of vinculin is expected to interact with the VBS of ␣-catenin (29,30), it is likely that vinculin localized at AJs also engages in actin binding, hence further reinforcing the connectivity between the cadherin-catenin complex and the F-actin. The strength of anchoring the AJ to the actin cytoskeleton can be dynamically regulated to match the actomyosin-generated tension by adjusting the polarized distribution of the cadherin-catenin complex (64), as well as the number of activated ␣-catenins and vinculins at AJs (Fig. 7B).…”

Mechanisms and mechanics of cell competition in epithelia

“…Within this framework, the contributions of cell growth, mitosis, apoptosis and cell intercalation (see the figure, panel c) are incorporated to predict the evolution of a tissue towards a stable mechanical equilibrium. It is important to note that this model ignores the mechanical contributions of cell-matrix adhesion 90 and centripetal cytoplasmic contractile activity 91 . Another limitation of most current vertex models is that they are restricted to two dimensions, although recent work suggests that three-dimensional modelling is possible 91 .…”

“…It is important to note that this model ignores the mechanical contributions of cell-matrix adhesion 90 and centripetal cytoplasmic contractile activity 91 . Another limitation of most current vertex models is that they are restricted to two dimensions, although recent work suggests that three-dimensional modelling is possible 91 . Despite these simplifications, vertex models have successfully represented biologically relevant processes 77,84,88,89,92 .…”