Capturing nematic order on tissue surfaces of arbitrary geometry.

A leading paradigm for understanding the large-scale behavior of tissues is via generalizations of liquid crystal physics; much like liquid crystals, tissues combine fluid-like, viscoelastic behaviors with local orientational order, such as nematic symmetry. Whilst aspects of quantitative agreement have been achieved for flat monolayers, the most striking features of tissue morphogenesis-including symmetry breaking, folding and invagination-concern surfaces with complex curved geometries in three dimensions. As yet, however, characterizing such behaviors has been frustrated due to the absence of proper image analysis methods; current state-of-the-art methods almost exclusively rely on two-dimensional intensity projections of multiple image planes, which superimpose data and lose geometric information that can be crucial.

New directions in epithelial mechanoadaptation.

Cells are active mechanical objects: they are subject to forces, exert force, and interpret changes in force as biological information. We now understand much about how this occurs at the molecular and single-cell level. We also appreciate that mechanobiology gains even greater complexity when it operates at the multicellular level of tissues and organisms.

BECLIN-1 is essential for the maintenance of gastrointestinal epithelial integrity by regulating endocytic trafficking, F-actin organization, and lysosomal function.

Disrupted intestinal homeostasis and barrier function contribute to the development of diseases such as inflammatory bowel disease. BECLIN-1, a core component of two class III phosphatidylinositol 3 kinase complexes, has a dual role in autophagy and endocytic trafficking. Emerging evidence suggests that its endocytic trafficking function is essential for intestinal integrity.

Adherens junctions co-opt EGFR-ERK signaling for epithelial mechanotransduction.

In this issue of , Houtekamer . report a mechanism by which adherens junctions enable epithelia to respond to mechanical stress. They demonstrate that E-cadherin-containing adhesions stimulate ERK signaling in response to tissue tension through a metalloproteinase pathway that releases EGF receptor ligands.

Viscous dissipation in the rupture of cell-cell contacts.

Cell-cell adhesions mediated by adherens junctions, structures connecting cells to each other and to the cortical cytoskeleton, are essential for epithelial physical and biological integrity. Nonetheless, how such structures resist mechanical stimuli that prompt cell-cell rupture is still not fully understood. Here we challenge the conventional views on cell-cell adhesion stability, highlighting the importance of viscous dissipation at the cellular level.

Advecting scaffolds: Controlling the remodeling of actomyosin with anillin.

We propose and analyze an active hydrodynamic theory that characterizes the effects of the scaffold protein anillin. Anillin is found at major sites of cortical activity, such as adherens junctions and the cytokinetic furrow, where the canonical regulator of actomyosin remodeling is the small GTPase, RhoA. RhoA acts via intermediary "effectors" to increase both the rates of activation of myosin motors and the polymerization of actin filaments.

Pyroptotic cell corpses are crowned with F-actin-rich filopodia that engage CLEC9A signaling in incoming dendritic cells.

While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia.

The desmosome-intermediate filament system facilitates mechanotransduction at adherens junctions for epithelial homeostasis.

Epithelial homeostasis can be critically influenced by how cells respond to mechanical forces, both local changes in force balance between cells and altered tissue-level forces. Coupling of specialized cell-cell adhesions to their cytoskeletons provides epithelia with diverse strategies to respond to mechanical stresses. Desmosomes confer tissue resilience when their associated intermediate filaments (IFs) stiffen in response to strain, while mechanotransduction associated with the E-cadherin apparatus at adherens junctions (AJs) actively modulates actomyosin by RhoA signaling.

A truncation mutant of adenomatous polyposis coli impairs apical cell extrusion through elevated epithelial tissue tension.

Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighboring cells and the extracellular matrix. Emerging evidence indicates that an imbalance in such forces can influence structural organization, homeostasis, and potentially contribute to disease. For instance, heightened tissue tension can impede apical cell extrusion, leading to the retention of apoptotic or transformed cells.

A Lifeact-EGFP quail for studying actin dynamics in vivo.

Here, we report the generation of a transgenic Lifeact-EGFP quail line for the investigation of actin organization and dynamics during morphogenesis in vivo. This transgenic avian line allows for the high-resolution visualization of actin structures within the living embryo, from the subcellular filaments that guide cell shape to the supracellular assemblies that coordinate movements across tissues. The unique suitability of avian embryos to live imaging facilitates the investigation of previously intractable processes during embryogenesis.

c-Src-induced vascular malformations require localised matrix degradation at focal adhesions.

Endothelial cells lining the blood vessel wall communicate intricately with the surrounding extracellular matrix, translating mechanical cues into biochemical signals. Moreover, vessels require the capability to enzymatically degrade the matrix surrounding them, to facilitate vascular expansion. c-Src plays a key role in blood vessel growth, with its loss in the endothelium reducing vessel sprouting and focal adhesion signalling.

BECLIN1 is essential for intestinal homeostasis involving autophagy-independent mechanisms through its function in endocytic trafficking.

Autophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and endocytic trafficking. Here we show intestinal epithelium-specific BECLIN1 deletion in adult mice leads to rapid fatal enteritis with compromised gut barrier integrity, highlighting its intrinsic critical role in gut maintenance.

Adherens junctions as molecular regulators of emergent tissue mechanics.

Tissue and organ development during embryogenesis relies on the collective and coordinated action of many cells. Recent studies have revealed that tissue material properties, including transitions between fluid and solid tissue states, are controlled in space and time to shape embryonic structures and regulate cell behaviours. Although the collective cellular flows that sculpt tissues are guided by tissue-level physical changes, these ultimately emerge from cellular-level and subcellular-level molecular mechanisms.

Preexisting tissue mechanical hypertension at adherens junctions disrupts apoptotic extrusion in epithelia.

Apical extrusion is a tissue-intrinsic process that allows epithelia to eliminate unfit or surplus cells. This is exemplified by the early extrusion of apoptotic cells, which is critical to maintain the epithelial barrier and prevent inflammation. Apoptotic extrusion is an active mechanical process, which involves mechanotransduction between apoptotic cells and their neighbors, as well as local changes in tissue mechanics.

Caveola mechanotransduction reinforces the cortical cytoskeleton to promote epithelial resilience.

As physical barriers, epithelia must preserve their integrity when challenged by mechanical stresses. Cell-cell junctions linked to the cortical cytoskeleton play key roles in this process, often with mechanotransduction mechanisms that reinforce tissues. Caveolae are mechanosensitive organelles that buffer tension via disassembly.

Apical extrusion prevents apoptosis from activating an acute inflammatory program in epithelia.

Apoptosis is traditionally considered to be an immunologically silent form of cell death. Multiple mechanisms exist to ensure that apoptosis does not stimulate the immune system to cause inflammation or autoimmunity. Against this expectation, we now report that epithelia are programmed to provoke, rather than suppress, inflammation in response to apoptosis.

An E-cadherin-actin clutch translates the mechanical force of cortical flow for cell-cell contact to inhibit epithelial cell locomotion.

Adherens junctions (AJs) allow cell contact to inhibit epithelial migration yet also permit epithelia to move as coherent sheets. How, then, do cells identify which contacts will inhibit locomotion? Here, we show that in human epithelial cells this arises from the orientation of cortical flows at AJs. When the leader cells from different migrating sheets make head-on contact with one another, they assemble AJs that couple together oppositely directed cortical flows.

Desmosome-anchored intermediate filaments facilitate tension-sensitive RhoA signaling for epithelial homeostasis.

Epithelia are subject to diverse forms of mechanical stress during development and post-embryonic life. They possess multiple mechanisms to preserve tissue integrity against tensile forces, which characteristically involve specialized cell-cell adhesion junctions coupled to the cytoskeleton. Desmosomes connect to intermediate filaments (IF) via desmoplakin (DP), while the E-cadherin complex links to the actomyosin cytoskeleton in adherens junctions (AJ).

Protocol to transfer epithelial acini between different extracellular matrices and orient fibril organization.

Extracellular matrix (ECM) provides fundamental support for epithelial tissues and controls cell function. The chemistry and mechanical properties of ECM components, including stiffness, elasticity, and fibrillar organization, influence epithelial tissue responses. Here we present a protocol describing the culture and transfer of epithelial acini from Matrigel to collagen gel and an approach to axially align the collagen fibrils by the external gel stretching.

Dynamically regulated focal adhesions coordinate endothelial cell remodelling in developing vasculature.

The assembly of a mature vascular network involves coordinated endothelial cell (EC) shape changes, including the process of EC elongation. How EC elongation is dynamically regulated in vivo is not fully understood. Here, we have generated a zebrafish mutant that is deficient for the integrin adaptor protein Talin 1 (Tln1).