scholarly journals Integration of contractile forces during tissue invagination

2010 ◽  
Vol 188 (5) ◽  
pp. 735-749 ◽  
Author(s):  
Adam C. Martin ◽  
Michael Gelbart ◽  
Rodrigo Fernandez-Gonzalez ◽  
Matthias Kaschube ◽  
Eric F. Wieschaus
Keyword(s):  
Cell Shape ◽  
Control Cell ◽  
Adherens Junction ◽  
Tissue Level ◽  
Epithelial Morphogenesis ◽  
Apical Constriction ◽  
Contractile Forces ◽  
Actomyosin Cytoskeleton ◽  
Cellular Forces ◽  
Anterior Posterior

Contractile forces generated by the actomyosin cytoskeleton within individual cells collectively generate tissue-level force during epithelial morphogenesis. During Drosophila mesoderm invagination, pulsed actomyosin meshwork contractions and a ratchet-like stabilization of cell shape drive apical constriction. Here, we investigate how contractile forces are integrated across the tissue. Reducing adherens junction (AJ) levels or ablating actomyosin meshworks causes tissue-wide epithelial tears, which release tension that is predominantly oriented along the anterior–posterior (a-p) embryonic axis. Epithelial tears allow cells normally elongated along the a-p axis to constrict isotropically, which suggests that apical constriction generates anisotropic epithelial tension that feeds back to control cell shape. Epithelial tension requires the transcription factor Twist, which stabilizes apical myosin II, promoting the formation of a supracellular actomyosin meshwork in which radial actomyosin fibers are joined end-to-end at spot AJs. Thus, pulsed actomyosin contractions require a supracellular, tensile meshwork to transmit cellular forces to the tissue level during morphogenesis.

scholarly journals The Drosophila afadin homologue Canoe regulates linkage of the actin cytoskeleton to adherens junctions during apical constriction

2009 ◽  
Vol 186 (1) ◽  
pp. 57-73 ◽  
Author(s):  
Jessica K. Sawyer ◽  
Nathan J. Harris ◽  
Kevin C. Slep ◽  
Ulrike Gaul ◽  
Mark Peifer
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Shape ◽  
Shape Change ◽  
Adherens Junctions ◽  
Apical Constriction ◽  
Cell Shape Change ◽  
Mediate Cell Adhesion ◽  
Mediate Cell ◽  
Actomyosin Cytoskeleton ◽  
Core Part

Cadherin-based adherens junctions (AJs) mediate cell adhesion and regulate cell shape change. The nectin–afadin complex also localizes to AJs and links to the cytoskeleton. Mammalian afadin has been suggested to be essential for adhesion and polarity establishment, but its mechanism of action is unclear. In contrast, Drosophila melanogaster’s afadin homologue Canoe (Cno) has suggested roles in signal transduction during morphogenesis. We completely removed Cno from embryos, testing these hypotheses. Surprisingly, Cno is not essential for AJ assembly or for AJ maintenance in many tissues. However, morphogenesis is impaired from the start. Apical constriction of mesodermal cells initiates but is not completed. The actomyosin cytoskeleton disconnects from AJs, uncoupling actomyosin constriction and cell shape change. Cno has multiple direct interactions with AJ proteins, but is not a core part of the cadherin–catenin complex. Instead, Cno localizes to AJs by a Rap1- and actin-dependent mechanism. These data suggest that Cno regulates linkage between AJs and the actin cytoskeleton during morphogenesis.

scholarly journals Dynamic myosin phosphorylation regulates contractile pulses and tissue integrity during epithelial morphogenesis

2014 ◽  
Vol 206 (3) ◽  
pp. 435-450 ◽  
Author(s):  
Claudia G. Vasquez ◽  
Mike Tworoger ◽  
Adam C. Martin
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
Epithelial Morphogenesis ◽  
Nonmuscle Myosin ◽  
Apical Constriction ◽  
Tissue Integrity ◽  
Cell Shape Change ◽  
Nonmuscle Myosin Ii ◽  
A Cell ◽  
Coupling Dynamic

Apical constriction is a cell shape change that promotes epithelial bending. Activation of nonmuscle myosin II (Myo-II) by kinases such as Rho-associated kinase (Rok) is important to generate contractile force during apical constriction. Cycles of Myo-II assembly and disassembly, or pulses, are associated with apical constriction during Drosophila melanogaster gastrulation. It is not understood whether Myo-II phosphoregulation organizes contractile pulses or whether pulses are important for tissue morphogenesis. Here, we show that Myo-II pulses are associated with pulses of apical Rok. Mutants that mimic Myo-II light chain phosphorylation or depletion of myosin phosphatase inhibit Myo-II contractile pulses, disrupting both actomyosin coalescence into apical foci and cycles of Myo-II assembly/disassembly. Thus, coupling dynamic Myo-II phosphorylation to upstream signals organizes contractile Myo-II pulses in both space and time. Mutants that mimic Myo-II phosphorylation undergo continuous, rather than incremental, apical constriction. These mutants fail to maintain intercellular actomyosin network connections during tissue invagination, suggesting that Myo-II pulses are required for tissue integrity during morphogenesis.

scholarly journals The adherens junction–associated LIM domain protein Smallish regulates epithelial morphogenesis

2018 ◽  
Vol 217 (3) ◽  
pp. 1079-1095 ◽  
Author(s):  
Hamze Beati ◽  
Irina Peek ◽  
Paulina Hordowska ◽  
Mona Honemann-Capito ◽  
Jade Glashauser ◽  
...  
Keyword(s):  
Planar Cell Polarity ◽  
Adherens Junction ◽  
Epithelial Morphogenesis ◽  
Lim Domain ◽  
Core Component ◽  
Apical Constriction ◽  
Binding Partner ◽  
Actomyosin Contractility ◽  
Lim Domain Protein ◽  
Embryonic Morphogenesis

In epithelia, cells adhere to each other in a dynamic fashion, allowing the cells to change their shape and move along each other during morphogenesis. The regulation of adhesion occurs at the belt-shaped adherens junction, the zonula adherens (ZA). Formation of the ZA depends on components of the Par–atypical PKC (Par-aPKC) complex of polarity regulators. We have identified the Lin11, Isl-1, Mec-3 (LIM) protein Smallish (Smash), the orthologue of vertebrate LMO7, as a binding partner of Bazooka/Par-3 (Baz), a core component of the Par-aPKC complex. Smash also binds to Canoe/Afadin and the tyrosine kinase Src42A and localizes to the ZA in a planar polarized fashion. Animals lacking Smash show loss of planar cell polarity (PCP) in the embryonic epidermis and reduced cell bond tension, leading to severe defects during embryonic morphogenesis of epithelial tissues and organs. Overexpression of Smash causes apical constriction of epithelial cells. We propose that Smash is a key regulator of morphogenesis coordinating PCP and actomyosin contractility at the ZA.

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 A contractile actomyosin network linked to adherens junctions by Canoe/afadin helps drive convergent extension

2011 ◽  
Vol 22 (14) ◽  
pp. 2491-2508 ◽  
Author(s):  
Jessica K. Sawyer ◽  
Wangsun Choi ◽  
Kuo-Chen Jung ◽  
Li He ◽  
Nathan J. Harris ◽  
...  
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
Adherens Junction ◽  
Tissue Level ◽  
The Body ◽  
Convergent Extension ◽  
Planar Polarity ◽  
Cell Shape Change ◽  
Apical Polarity ◽  
Polarity Proteins

Integrating individual cell movements to create tissue-level shape change is essential to building an animal. We explored mechanisms of adherens junction (AJ):cytoskeleton linkage and roles of the linkage regulator Canoe/afadin during Drosophila germband extension (GBE), a convergent-extension process elongating the body axis. We found surprising parallels between GBE and a quite different morphogenetic movement, mesoderm apical constriction. Germband cells have an apical actomyosin network undergoing cyclical contractions. These coincide with a novel cell shape change—cell extension along the anterior–posterior (AP) axis. In Canoe's absence, GBE is disrupted. The apical actomyosin network detaches from AJs at AP cell borders, reducing coordination of actomyosin contractility and cell shape change. Normal GBE requires planar polarization of AJs and the cytoskeleton. Canoe loss subtly enhances AJ planar polarity and dramatically increases planar polarity of the apical polarity proteins Bazooka/Par3 and atypical protein kinase C. Changes in Bazooka localization parallel retraction of the actomyosin network. Globally reducing AJ function does not mimic Canoe loss, but many effects are replicated by global actin disruption. Strong dose-sensitive genetic interactions between canoe and bazooka are consistent with them affecting a common process. We propose a model in which an actomyosin network linked at AP AJs by Canoe and coupled to apical polarity proteins regulates convergent extension.

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 Spectrin couples cell shape, cortical tension, and Hippo signaling in retinal epithelial morphogenesis

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Hua Deng ◽  
Limin Yang ◽  
Pei Wen ◽  
Huiyan Lei ◽  
Paul Blount ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Shape ◽  
Myosin Ii ◽  
Epithelial Morphogenesis ◽  
Hippo Signaling ◽  
Membrane Domains ◽  
Apical Constriction ◽  
Cortical Tension ◽  
Mutant Cells ◽  
Apical Area

Although extracellular force has a profound effect on cell shape, cytoskeleton tension, and cell proliferation through the Hippo signaling effector Yki/YAP/TAZ, how intracellular force regulates these processes remains poorly understood. Here, we report an essential role for spectrin in specifying cell shape by transmitting intracellular actomyosin force to cell membrane. While activation of myosin II in Drosophila melanogaster pupal retina leads to increased cortical tension, apical constriction, and Yki-mediated hyperplasia, spectrin mutant cells, despite showing myosin II activation and Yki-mediated hyperplasia, paradoxically display decreased cortical tension and expanded apical area. Mechanistically, we show that spectrin is required for tethering cortical F-actin to cell membrane domains outside the adherens junctions (AJs). Thus, in the absence of spectrin, the weakened attachment of cortical F-actin to plasma membrane results in a failure to transmit actomyosin force to cell membrane, causing an expansion of apical surfaces. These results uncover an essential mechanism that couples cell shape, cortical tension, and Hippo signaling and highlight the importance of non–AJ membrane domains in dictating cell shape in tissue morphogenesis.

scholarly journals Charting the unknown currents of cellular flows and forces

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev186403 ◽  
Author(s):  
Christian Dahmann ◽  
Anne-Kathrin Classen
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
Tissue Level ◽  
Tissue Mechanics ◽  
Epithelial Morphogenesis ◽  
Mechanical Forces ◽  
Cell Behaviors ◽  
Cell Shape Change ◽  
Active Generation ◽  
Correct Size

ABSTRACTOne of the central questions in developmental biology concerns how cells become organized into tissues of the correct size, shape and polarity. This organization depends on the implementation of a cell's genetic information to give rise to specific and coordinated cell behaviors, including cell division and cell shape change. The execution of these cell behaviors requires the active generation of mechanical forces. However, understanding how force generation is controlled and, importantly, coordinated among many cells in a tissue was little explored until the early 2000s. Suzanne Eaton was one of the pioneers in this emerging field of developmental tissue mechanics. As we briefly review here, she connected the quantitative analysis of cell behaviors with genetic assays, and integrated physical modeling with measurements of mechanical forces to reveal fundamental insights into epithelial morphogenesis at cell- and tissue-level scales.

scholarly journals Abl suppresses cell extrusion and intercalation during epithelium folding

2016 ◽  
Vol 27 (18) ◽  
pp. 2822-2832 ◽  
Author(s):  
Jeanne N. Jodoin ◽  
Adam C. Martin
Keyword(s):  
Cell Shape ◽  
Epithelial To Mesenchymal Transition ◽  
Adherens Junction ◽  
Apical Constriction ◽  
Mesenchymal Transition ◽  
Abl Tyrosine Kinase ◽  
Cell Intercalation ◽  
Shape Changes ◽  
Insight Into ◽  
Cell Extrusion

Tissue morphogenesis requires control over cell shape changes and rearrangements. In the Drosophila mesoderm, linked epithelial cells apically constrict, without cell extrusion or intercalation, to fold the epithelium into a tube that will then undergo epithelial-to-mesenchymal transition (EMT). Apical constriction drives tissue folding or cell extrusion in different contexts, but the mechanisms that dictate the specific outcomes are poorly understood. Using live imaging, we found that Abelson (Abl) tyrosine kinase depletion causes apically constricting cells to undergo aberrant basal cell extrusion and cell intercalation. abl depletion disrupted apical–basal polarity and adherens junction organization in mesoderm cells, suggesting that extruding cells undergo premature EMT. The polarity loss was associated with abnormal basolateral contractile actomyosin and Enabled (Ena) accumulation. Depletion of the Abl effector Enabled (Ena) in abl-depleted embryos suppressed the abl phenotype, consistent with cell extrusion resulting from misregulated ena. Our work provides new insight into how Abl loss and Ena misregulation promote cell extrusion and EMT.

scholarly journals Uncoupling apical constriction from tissue invagination

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
SeYeon Chung ◽  
Sangjoon Kim ◽  
Deborah J Andrew
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
Rho Kinase ◽  
Tissue Level ◽  
Tube Formation ◽  
Intrinsic Properties ◽  
Apical Constriction ◽  
Cell Shape Change ◽  
Polarized Epithelia ◽  
Muscle Myosin

Apical constriction is a widely utilized cell shape change linked to folding, bending and invagination of polarized epithelia. It remains unclear how apical constriction is regulated spatiotemporally during tissue invagination and how this cellular process contributes to tube formation in different developmental contexts. Using Drosophila salivary gland (SG) invagination as a model, we show that regulation of folded gastrulation expression by the Fork head transcription factor is required for apicomedial accumulation of Rho kinase and non-muscle myosin II, which coordinate apical constriction. We demonstrate that neither loss of spatially coordinated apical constriction nor its complete blockage prevent internalization and tube formation, although such manipulations affect the geometry of invagination. When apical constriction is disrupted, compressing force generated by a tissue-level myosin cable contributes to SG invagination. We demonstrate that fully elongated polarized SGs can form outside the embryo, suggesting that tube formation and elongation are intrinsic properties of the SG.

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