scholarly journals Regulation of tensile stress in response to external forces coordinates epithelial cell shape transitions with organ growth and elongation

2018 ◽  
Author(s):  
Ramya Balaji ◽  
Vanessa Weichselberger ◽  
Anne-Kathrin Classen
Keyword(s):  
Epithelial Cell ◽  
Cell Shape ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Apical Surface ◽  
Nurse Cells ◽  
Cuboidal Cell ◽  
Cell Shapes ◽  
External Forces ◽  
Shape Transitions

AbstractThe role of actomyosin contractility at epithelial adherens junctions has been extensively studied. However, little is known about how external forces are integrated to establish epithelial cell and organ shape in vivo. We use the Drosophila follicle epithelium to investigate how tension at adherens junctions is regulated to integrate external forces arising from changes in germline size and shape. We find that overall tension in the epithelium decreases despite pronounced growth of enclosed germline cells, suggesting that the epithelium relaxes to accommodate growth. However, we find local differences in adherens junction tension correlate with apposition to germline nurse cells or the oocyte. We demonstrate that medial Myosin II coupled to corrugating adherens junctions resists nurse cell-derived forces and thus maintains apical surface areas and cuboidal cell shapes. Furthermore, medial reinforcement of the apical surface ensures cuboidal-to-columnar cell shape transitions and imposes circumferential constraints on nurse cells guiding organ elongation. Our study provides insight into how tension within an adherens junction network integrates growth of a neighbouring tissue, mediates cell shape transitions and channels growth into organ elongation.

scholarly journals Cell Polarity Development and Protein Trafficking in Hepatocytes Lacking E-Cadherin/β-Catenin–based Adherens Junctions

2007 ◽  
Vol 18 (6) ◽  
pp. 2313-2321 ◽  
Author(s):  
Delphine Théard ◽  
Magdalena Steiner ◽  
Dharamdajal Kalicharan ◽  
Dick Hoekstra ◽  
Sven C.D. van IJzendoorn
Keyword(s):  
Cell Polarity ◽  
Membrane Trafficking ◽  
Protein Trafficking ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Apical Surface ◽  
Tight Junction Formation ◽  
E Cadherin

Using a mutant hepatocyte cell line in which E-cadherin and β-catenin are completely depleted from the cell surface, and, consequently, fail to form adherens junctions, we have investigated adherens junction requirement for apical–basolateral polarity development and polarized membrane trafficking. It is shown that these hepatocytes retain the capacity to form functional tight junctions, develop full apical–basolateral cell polarity, and assemble a subapical cortical F-actin network, although with a noted delay and a defect in subsequent apical lumen remodeling. Interestingly, whereas hepatocytes typically target the plasma membrane protein dipeptidyl peptidase IV first to the basolateral surface, followed by its transcytosis to the apical domain, hepatocytes lacking E-cadherin–based adherens junctions target dipeptidyl peptidase IV directly to the apical surface. Basolateral surface-directed transport of other proteins or lipids tested was not visibly affected in hepatocytes lacking E-cadherin–based adherens junctions. Together, our data show that E-cadherin/β-catenin–based adherens junctions are dispensable for tight junction formation and apical lumen biogenesis but not for apical lumen remodeling. In addition, we suggest a possible requirement for E-cadherin/β-catenin–based adherens junctions with regard to the indirect apical trafficking of specific proteins in hepatocytes.

scholarly journals The Biomechanical Basis of Biased Epithelial Tube Elongation

2020 ◽  
Author(s):  
Steve Runser ◽  
Lisa Conrad ◽  
Harold Gómez ◽  
Christine Lang ◽  
Mathilde Dumond ◽  
...  
Keyword(s):  
Shear Stress ◽  
Growth Factor ◽  
Cell Shape ◽  
Kidney Development ◽  
Longitudinal Direction ◽  
Apical Surface ◽  
Division Plane ◽  
Cell Shapes ◽  
A Cell ◽  
Epithelial Tubes

ABSTRACTDuring lung development, epithelial branches expand preferentially in longitudinal direction. This bias in outgrowth has been linked to a bias in cell shape and in the cell division plane. How such bias arises is unknown. Here, we show that biased epithelial outgrowth occurs independent of the surrounding mesenchyme. Biased outgrowth is also not the consequence of a growth factor gradient, as biased outgrowth is obtained with uniform growth factor cultures, and in the presence of the FGFR inhibitor SU5402. Furthermore, we note that epithelial tubes are largely closed during early lung and kidney development. By simulating the reported fluid flow inside segmented narrow epithelial tubes, we show that the shear stress levels on the apical surface are sufficient to explain the reported bias in cell shape and outgrowth. We use a cell-based vertex model to confirm that apical shear forces, unlike constricting forces, can give rise to both the observed bias in cell shapes and tube elongation. We conclude that shear stress may be a more general driver of biased tube elongation beyond its established role in angiogenesis.

scholarly journals Microtubules stabilize intercellular contractile force transmission during tissue folding

2019 ◽  
Author(s):  
Clint S. Ko ◽  
Vardges Tserunyan ◽  
Adam C. Martin
Keyword(s):  
Cell Shape ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Contractile Force ◽  
Force Transmission ◽  
Microtubule Network ◽  
Apical Constriction ◽  
Actomyosin Contractility ◽  
Actomyosin Contraction ◽  
Stable Connection

AbstractDuring development, forces transmitted between cells are critical for sculpting epithelial tissues. Actomyosin contractility in the middle of the cell apex (medioapical) can change cell shape (e.g., apical constriction), but can also result in force transmission between cells via attachments to adherens junctions. How actomyosin networks maintain attachments to adherens junctions under tension is poorly understood. Here, we discovered that microtubules stabilize actomyosin intercellular attachments in epithelia during Drosophila mesoderm invagination. First, we used live imaging to show a novel arrangement of the microtubule cytoskeleton during apical constriction: medioapical, non-centrosomal Patronin (CAMSAP) foci formed by actomyosin contraction organizes an apical microtubule network. Microtubules were required for mesoderm invagination but were not necessary for apical contractility or adherens junction assembly. Instead, microtubules promoted the stable connection between medioapical actomyosin and adherens junctions. These results define a role for coordination between actin and microtubule cytoskeletal systems in intercellular force transmission and tissue morphogenesis.

scholarly journals Anisotropy links cell shapes to a solid-to-fluid transition during convergent extension

2019 ◽  
Author(s):  
Xun Wang ◽  
Matthias Merkel ◽  
Leo B. Sutter ◽  
Gonca Erdemci-Tandogan ◽  
M. Lisa Manning ◽  
...  
Keyword(s):  
Cell Shape ◽  
Shape Index ◽  
Convergent Extension ◽  
Cell Alignment ◽  
Cell Rearrangement ◽  
Internal Cell ◽  
Cell Patterns ◽  
Cell Shapes ◽  
Tissue Reorganization ◽  
External Forces

AbstractWithin developing embryos, tissues flow and reorganize dramatically on timescales as short as minutes. This includes epithelial tissues, which often narrow and elongate in convergent extension movements due to anisotropies in external forces or in internal cell-generated forces. However, the mechanisms that allow or prevent tissue reorganization, especially in the presence of strongly anisotropic forces, remain unclear. We study this question in the converging and extending Drosophila germband epithelium, which displays planar polarized myosin II and experiences anisotropic forces from neighboring tissues, and we show that in contrast to isotropic tissues, cell shape alone is not sufficient to predict the onset of rapid cell rearrangement. From theoretical considerations and vertex model simulations, we predict that in anisotropic tissues two experimentally accessible metrics of cell patterns—the cell shape index and a cell alignment index—are required to determine whether an anisotropic tissue is in a solid-like or fluid-like state. We show that changes in cell shape and alignment over time in the Drosophila germband indicate a solid-to-fluid transition that corresponds to the onset of cell rearrangement and convergent extension in wild-type embryos and are also consistent with more solid-like behavior in bnt mutant embryos. Thus, the onset of cell rearrangement in the germband can be predicted by a combination of cell shape and alignment. These findings suggest that convergent extension is associated with a transition to more fluid-like tissue behavior, which may help accommodate tissue shape changes during rapid developmental events.

Real-time imaging of cell-cell adherens junctions reveals that Drosophila mesoderm invagination begins with two phases of apical constriction of cells

2001 ◽  
Vol 114 (3) ◽  
pp. 493-501 ◽  
Author(s):  
H. Oda ◽  
S. Tsukita
Keyword(s):  
Real Time ◽  
Cell Shape ◽  
Adherens Junctions ◽  
Cell Sheet ◽  
Apical Surface ◽  
Apical Constriction ◽  
Real Time Imaging ◽  
Cell Shape Changes ◽  
Shape Changes ◽  
Cell Cell

Invagination of the epithelial cell sheet of the prospective mesoderm in Drosophila gastrulation is a well-studied, relatively simple morphogenetic event that results from dynamic cell shape changes and cell movements. However, these cell behaviors have not been followed at a sufficiently short time resolution. We examined mesoderm invagination in living wild-type embryos by real-time imaging of fluorescently labeled cell-cell adherens junctions, which are located at the apical zones of cell-cell contact. Low-light fluorescence video microscopy directly visualized the onset and progression of invagination. In an initial period of approximately 2 minutes, cells around the ventral midline reduced their apical surface areas slowly in a rather synchronous manner. Next, the central and more lateral cells stochastically accelerated or initiated their apical constriction, giving rise to random arrangements of cells with small and relatively large apices. Thus, we found that mesoderm invagination began with slow synchronous and subsequent fast stochastic phases of cell apex constriction. Furthermore, we showed that the mesoderm invagination of folded gastrulation mutant embryos lacked the normal two constriction phases, and instead began with asynchronous, feeble cell shape changes. Our observations suggested that Folded gastrulation-mediated signaling enabled synchronous activation of the contractile cortex, causing competition among the individual mesodermal cells for apical constriction. Movies available on-line: http://www.biologists.com/JCS/movies/jcs2073.html

scholarly journals Microtubules promote intercellular contractile force transmission during tissue folding

2019 ◽  
Vol 218 (8) ◽  
pp. 2726-2742 ◽  
Author(s):  
Clint S. Ko ◽  
Vardges Tserunyan ◽  
Adam C. Martin
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Shape ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Contractile Force ◽  
Force Transmission ◽  
Microtubule Network ◽  
Apical Constriction ◽  
Actomyosin Contractility ◽  
Actomyosin Contraction

During development, forces transmitted between cells are critical for sculpting epithelial tissues. Actomyosin contractility in the middle of the cell apex (medioapical) can change cell shape (e.g., apical constriction) but can also result in force transmission between cells via attachments to adherens junctions. How actomyosin networks maintain attachments to adherens junctions under tension is poorly understood. Here, we discovered that microtubules promote actomyosin intercellular attachments in epithelia during Drosophila melanogaster mesoderm invagination. First, we used live imaging to show a novel arrangement of the microtubule cytoskeleton during apical constriction: medioapical Patronin (CAMSAP) foci formed by actomyosin contraction organized an apical noncentrosomal microtubule network. Microtubules were required for mesoderm invagination but were not necessary for initiating apical contractility or adherens junction assembly. Instead, microtubules promoted connections between medioapical actomyosin and adherens junctions. These results delineate a role for coordination between actin and microtubule cytoskeletal systems in intercellular force transmission during tissue morphogenesis.

scholarly journals PTP-PEST controls motility, adherens junction assembly, and Rho GTPase activity in colon cancer cells

2010 ◽  
Vol 299 (2) ◽  
pp. C454-C463 ◽  
Author(s):  
Rosario Espejo ◽  
William Rengifo-Cam ◽  
Michael D. Schaller ◽  
B. Mark Evers ◽  
Sarita K. Sastry
Keyword(s):  
Epithelial Cell ◽  
Cell Motility ◽  
Colon Carcinoma ◽  
Rho Gtpase ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Carcinoma Cells ◽  
Gtpase Activity ◽  
Colon Carcinoma Cells ◽  
Cell Cell

An important step in carcinoma progression is loss of cell-cell adhesion leading to increased invasion and metastasis. We show here that the protein tyrosine phosphatase, PTP-PEST, is a critical regulator of cell-cell junction integrity and epithelial cell motility. Using colon carcinoma cells, we show that the expression level of PTP-PEST regulates cell motility. Either transient small interfering RNA or stable short hairpin RNA knockdown of PTP-PEST enhances haptotactic and chemotactic migration of KM12C colon carcinoma cells. Furthermore, KM12C cells with stably knocked down PTP-PEST exhibit a mesenchymal-like phenotype with prominent membrane ruffles and lamellae. In contrast, ectopic expression of PTP-PEST in KM20 or DLD-1 cells, which lack detectable endogenous PTP-PEST expression, suppresses haptotactic migration. Importantly, we find that PTP-PEST localizes in adherens junctions. Concomitant with enhanced motility, stable knockdown of PTP-PEST causes a disruption of cell-cell junctions. These effects are due to a defect in junctional assembly and not to a loss of E-cadherin expression. Adherens junction assembly is impaired following calcium switch in KM12C cells with stably knocked down PTP-PEST and is accompanied by an increase in the activity of Rac1 and a suppression of RhoA activity in response to cadherin engagement. Taken together, these results suggest that PTP-PEST functions as a suppressor of epithelial cell motility by controlling Rho GTPase activity and the assembly of adherens junctions.

scholarly journals Mechanosensitive EPLIN-dependent remodeling of adherens junctions regulates epithelial reshaping

2011 ◽  
Vol 194 (4) ◽  
pp. 643-656 ◽  
Author(s):  
Katsutoshi Taguchi ◽  
Takashi Ishiuchi ◽  
Masatoshi Takeichi
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Mechanical Forces ◽  
Cell Adhesions ◽  
Cell Cell

The zonula adherens (ZA), a type of adherens junction (AJ), plays a major role in epithelial cell–cell adhesions. It remains unknown how the ZA is remodeled during epithelial reorganization. Here we found that the ZA was converted to another type of AJ with punctate morphology (pAJ) at the margins of epithelial colonies. The F-actin–stabilizing protein EPLIN (epithelial protein lost in neoplasm), which functions to maintain the ZA via its association with αE-catenin, was lost in the pAJs. Consistently, a fusion of αE-catenin and EPLIN contributed to the formation of ZA but not pAJs. We show that junctional tension was important for retaining EPLIN at AJs, and another force derived from actin fibers laterally attached to the pAJs inhibited EPLIN–AJ association. Vinculin was required for general AJ formation, and it cooperated with EPLIN to maintain the ZA. These findings suggest that epithelial cells remodel their junctional architecture by responding to mechanical forces, and the αE-catenin–bound EPLIN acts as a mechanosensitive regulator for this process.

scholarly journals Independent apical and basal mechanical systems determine cell and tissue shape in the Drosophila wing disc

2020 ◽  
Author(s):  
Amarendra Badugu ◽  
Andres Käch
Keyword(s):  
Basement Membrane ◽  
Drug Treatment ◽  
Cell Shape ◽  
Membrane Integrity ◽  
Wing Disc ◽  
Tissue Mechanics ◽  
Membrane Thickness ◽  
Apical Surface ◽  
Basement Membrane Thickness ◽  
Cell Shapes

AbstractHow cell shape and mechanics are organized in three dimensions during tissue morphogenesis is poorly understood. In the Drosophila wing imaginal disc, we examined the mechanical processes that determine the shape of epithelial cells. Since it has been known that basement membrane influences the mechanics intracellularly, we reexamined the material properties of the basement membrane with fluorescence and transmission electron microscopy in its native environment. Further, we investigated the effect on cell shape and tissue mechanics when disruptions were instigated at three different time scales: (1) short (seconds with laser cutting), (2) medium (minutes with drug treatments), and (3) long (days with RNAi interference). We found regions in which the basement membrane is much thicker and heterogeneous than previously reported. Disrupting the actin cytoskeleton through drug treatment affects cell shape only at the apical surface, while the shapes in the medial and basal surfaces were not altered. In contrast, when integrin function was inhibited via RNAi or basement membrane integrity was disrupted by drug treatment, the medial and basal cell shapes were affected. We propose that basement membrane thickness patterns determine the height and basal surface area of cells and the curvature of folds in the wing disc. Based on these findings and previous studies, we propose a model of how cell shapes and tissue properties were determined by highly local, modular apical and basal mechanics.Graphical abstract

scholarly journals Theory of Epithelial Cell Shape Transitions Induced by Mechanoactive Chemical Gradients

2018 ◽  
Vol 114 (4) ◽  
pp. 968-977 ◽  
Author(s):  
Kinjal Dasbiswas ◽  
Edouard Hannezo ◽  
Nir S. Gov
Keyword(s):  
Epithelial Cell ◽  
Cell Shape ◽  
Chemical Gradients ◽  
Shape Transitions
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