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 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 LMO7-dependent apical constriction requires the binding of the Myosin heavy chain

2021 ◽  
Author(s):  
Miho Matsuda ◽  
Chih-Wen Chu ◽  
Sergei S Sokol
Keyword(s):  
Heavy Chain ◽  
Myosin Light Chain ◽  
Myosin Ii ◽  
Tube Formation ◽  
Epithelial Morphogenesis ◽  
Apical Constriction ◽  
Actomyosin Contractility ◽  
Apical Domain ◽  
Underlying Mechanisms ◽  
Muscle Myosin

The reduction of the apical domain, or apical constriction, is a process that occurs in a single cell or is coordinated in a group of cells in the epithelium. Coordinated apical constriction is particularly important when the epithelium is undergoing dynamic morphogenetic events such as furrow or tube formation. However, the underlying mechanisms remain incompletely understood. Here we show that Lim only protein 7 (Lmo7) is a novel activator of apical constriction in the Xenopus superficial ectoderm, which coordinates actomyosin contractility in a group of cells during epithelial morphogenesis. Like other apical constriction regulators, Lmo7 requires the activation of the Rho-Rock-Myosin II pathway to induce apical constriction. However, instead of increasing the phosphorylation of myosin light chain (MLC), Lmo7 binds muscle myosin II heavy chain A (NMIIA) and increases its association with actomyosin bundles at adherens junctions (AJs). Lmo7 overexpression modulates the subcellular distribution of Wtip, a tension marker at AJs, suggesting that Lmo7 generates mechanical forces at AJs. We propose that Lmo7 increases actomyosin contractility at AJs by promoting the formation of actomyosin bundles.

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 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 Cell non-autonomy amplifies disruption of neurulation by mosaic Vangl2 deletion

2020 ◽  
Author(s):  
Gabriel Galea ◽  
Eirini Maniou ◽  
Abigail R Marshall ◽  
Nicholas DE Greene ◽  
Andrew J Copp
Keyword(s):  
Planar Cell Polarity ◽  
Myosin Ii ◽  
Apical Cell ◽  
Neural Tube Closure ◽  
Congenital Defects ◽  
Cell Cortex ◽  
Core Component ◽  
Apical Constriction ◽  
Neuroepithelial Cells ◽  
Tube Closure

Abstract Post-zygotic mutations that generate tissue mosaicism are increasingly associated with severe congenital defects, including those arising from failed neural tube closure. We observed that elevation of the neural folds during mouse spinal neurulation is vulnerable to deletion of the planar cell polarity core component Van Gogh-like (Vangl)2 in as few as 16% of neuroepithelial cells. Vangl2-deleted cells are typically dispersed throughout the neuroepithelium, and each non-autonomously prevents apical constriction by an average of five Vangl2-replete neighbours. This inhibition of apical constriction involves reduced myosin-II recruitment to neighbour cell borders and shortening of basally-extending microtubule tails, which are known to facilitate apical constriction. Vangl2-deleted cells themselves continue to apically constrict and preferentially recruit myosin-II to their apical cell cortex rather than to apical cap sarcomere-like organisations. Such non-autonomous effects can explain how post-zygotic mutations affecting a minority of cells can cause catastrophic failure of morphogenesis leading to clinically important birth defects.

Proteomic identification of the LIM domain protein FHL1 as the gene-product mutated in reducing body myopathy

2009 ◽  
Vol 40 (01) ◽  
Author(s):  
J Schessl ◽  
Y Zou ◽  
MJ McGrath ◽  
BS Cowling ◽  
B Maiti ◽  
...  
Keyword(s):  
Gene Product ◽  
Lim Domain ◽  
Lim Domain Protein ◽  
Proteomic Identification ◽  
Domain Protein

scholarly journals Four-and-a-half LIM domain protein 2 (FHL2) deficiency protects mice from diet-induced obesity and high FHL2 expression marks human obesity

Metabolism ◽  
2021 ◽  
pp. 154815
Author(s):  
Maria P. Clemente-Olivo ◽  
Jayron J. Habibe ◽  
Mariska Vos ◽  
Roelof Ottenhoff ◽  
Aldo Jongejan ◽  
...  
Keyword(s):  
Lim Domain ◽  
Human Obesity ◽  
Diet Induced Obesity ◽  
Lim Domain Protein ◽  
Domain Protein

scholarly journals Lasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Denise Beckmann ◽  
Anja Römer-Hillmann ◽  
Annika Krause ◽  
Uwe Hansen ◽  
Corinna Wehmeyer ◽  
...  
Keyword(s):  
Joint Destruction ◽  
Adherens Junction ◽  
Metastatic Breast ◽  
Cellular Transformation ◽  
Tissue Formation ◽  
Tissue Remodelling ◽  
Binding Partner ◽  
Fibroblast Transformation ◽  
Fibroblast Like Synoviocytes

AbstractThe LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the aggressive transformation of cells is unclear. Here we use integrative epigenomic profiling of invasive fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and from mouse models of the disease, to identify Lasp1 as an epigenomically co-modified region in chronic inflammatory arthritis and a functionally important binding partner of the Cadherin-11/β-Catenin complex in zipper-like cell-to-cell contacts. In vitro, loss or blocking of Lasp1 alters pathological tissue formation, migratory behaviour and platelet-derived growth factor response of arthritic FLS. In arthritic human TNF transgenic mice, deletion of Lasp1 reduces arthritic joint destruction. Therefore, we show a function of Lasp1 in cellular junction formation and inflammatory tissue remodelling and identify Lasp1 as a potential target for treating inflammatory joint disorders associated with aggressive cellular transformation.

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