Segmentation and Tracking of Adherens Junctions in 3D for the Analysis of Epithelial Tissue Morphogenesis

Morphogenesis is a shape-building process during development of multicellular organisms. During this process the establishment and modulation of cell-cell contacts play an important role. Cadherins, the major cell adhesion molecules, form adherens junctions connecting epithelial cells. Numerous studies in Bilateria have shown that cadherins are associated with the regulation of cell differentiation, cell shape changes, cell migration and tissue morphogenesis. To date, the role of Cadherins in non-bilaterians is unknown. Here, we study the expression and the function of two paralogous classical cadherins, cadherin1 and cadherin3, in the diploblastic animal, the sea anemone Nematostella vectensis. We show that a cadherin switch is accompanying the formation of germ layers. Using specific antibodies, we show that both cadherins are localized to adherens junctions at apical and basal positions in ectoderm and endoderm. During gastrulation, partial EMT of endodermal cells is marked by a step-wise downregulation of cadherin3 and upregulation of cadherin1. Knockdown experiments show that both cadherins are required for maintenance of tissue integrity and tissue morphogenesis. This demonstrates that cnidarians convergently use cadherins to differentially control morphogenetic events during development.

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Connective-Tissue Fibroblasts Established on Micropillar Interfaces are Pivotal for Epithelial-Tissue Morphogenesis

Advanced Functional Materials ◽

10.1002/adfm.200890089 ◽

2008 ◽

Vol 18 (21) ◽

pp. NA-NA

Author(s):

Eva Mussig ◽

Thorsten Steinberg ◽

Simon Schulz ◽

Joachim P. Spatz ◽

Jens Ulmer ◽

...

Keyword(s):

Connective Tissue ◽

Epithelial Tissue ◽

Tissue Morphogenesis

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Adherens Junctions and Desmosomes Coordinate Mechanics and Signaling to Orchestrate Tissue Morphogenesis and Function: An Evolutionary Perspective

Cold Spring Harbor Perspectives in Biology ◽

10.1101/cshperspect.a029207 ◽

2017 ◽

Vol 10 (11) ◽

pp. a029207 ◽

Cited By ~ 35

Author(s):

Matthias Rübsam ◽

Joshua A. Broussard ◽

Sara A. Wickström ◽

Oxana Nekrasova ◽

Kathleen J. Green ◽

...

Keyword(s):

Adherens Junctions ◽

Evolutionary Perspective ◽

Tissue Morphogenesis ◽

And Function

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Polarized Protein Transport and Lumen Formation During Epithelial Tissue Morphogenesis

Annual Review of Cell and Developmental Biology ◽

10.1146/annurev-cellbio-100814-125323 ◽

2015 ◽

Vol 31 (1) ◽

pp. 575-591 ◽

Cited By ~ 32

Author(s):

Alex J. Blasky ◽

Anthony Mangan ◽

Rytis Prekeris

Keyword(s):

Protein Transport ◽

Epithelial Tissue ◽

Tissue Morphogenesis ◽

Lumen Formation

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Unified quantitative characterization of epithelial tissue development

eLife ◽

10.7554/elife.08519 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 87

Author(s):

Boris Guirao ◽

Stéphane U Rigaud ◽

Floris Bosveld ◽

Anaïs Bailles ◽

Jesús López-Gay ◽

...

Keyword(s):

Cell Shape ◽

Tissue Growth ◽

Epithelial Tissue ◽

Tissue Development ◽

Tissue Morphogenesis ◽

Quantitative Characterization ◽

Cell Shape Changes ◽

The Impact ◽

Shape Changes

Understanding the mechanisms regulating development requires a quantitative characterization of cell divisions, rearrangements, cell size and shape changes, and apoptoses. We developed a multiscale formalism that relates the characterizations of each cell process to tissue growth and morphogenesis. Having validated the formalism on computer simulations, we quantified separately all morphogenetic events in the Drosophila dorsal thorax and wing pupal epithelia to obtain comprehensive statistical maps linking cell and tissue scale dynamics. While globally cell shape changes, rearrangements and divisions all significantly participate in tissue morphogenesis, locally, their relative participations display major variations in space and time. By blocking division we analyzed the impact of division on rearrangements, cell shape changes and tissue morphogenesis. Finally, by combining the formalism with mechanical stress measurement, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our formalism provides a novel and rigorous approach to uncover mechanisms governing tissue development.

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Transition of responsive mechanosensitive elements from focal adhesions to adherens junctions on epithelial differentiation

Molecular Biology of the Cell ◽

10.1091/mbc.e17-06-0387 ◽

2018 ◽

Vol 29 (19) ◽

pp. 2317-2325 ◽

Cited By ~ 12

Author(s):

Barbara Noethel ◽

Lena Ramms ◽

Georg Dreissen ◽

Marco Hoffmann ◽

Ronald Springer ◽

...

Keyword(s):

Mechanical Stress ◽

Adherens Junctions ◽

Adhesion Formation ◽

Focal Adhesions ◽

Intercellular Junctions ◽

Cell Junctions ◽

Epithelial Tissue ◽

Cell Matrix ◽

Junction Protein ◽

Cell Cell

The skin’s epidermis is a multilayered epithelial tissue and the first line of defense against mechanical stress. Its barrier function depends on an integrated assembly and reorganization of cell–matrix and cell–cell junctions in the basal layer and on different intercellular junctions in suprabasal layers. However, how mechanical stress is recognized and which adhesive and cytoskeletal components are involved are poorly understood. Here, we subjected keratinocytes to cyclic stress in the presence or absence of intercellular junctions. Both states not only recognized but also responded to strain by reorienting actin filaments perpendicular to the applied force. Using different keratinocyte mutant strains that altered the mechanical link of the actin cytoskeleton to either cell–matrix or cell–cell junctions, we show that not only focal adhesions but also adherens junctions function as mechanosensitive elements in response to cyclic strain. Loss of paxillin or talin impaired focal adhesion formation and only affected mechanosensitivity in the absence but not presence of intercellular junctions. Further analysis revealed the adherens junction protein α-catenin as a main mechanosensor, with greatest sensitivity conferred on binding to vinculin. Our data reveal a mechanosensitive transition from cell–matrix to cell–cell adhesions on formation of keratinocyte monolayers with vinculin and α-catenin as vital players.

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Actomyosin contractility modulates Wnt signaling through adherens junction stability

10.1101/220178 ◽

2017 ◽

Cited By ~ 1

Author(s):

Eric T. Hall ◽

Elizabeth Hoesing ◽

Endre Sinkovics ◽

Esther M. Verheyen

Keyword(s):

Wnt Signaling ◽

Gene Transcription ◽

Target Gene ◽

Nuclear Translocation ◽

Adherens Junctions ◽

Wnt Signaling Pathway ◽

Epithelial Tissue ◽

Actomyosin Contractility ◽

Target Gene Transcription ◽

E Cadherin

AbstractMechanical forces can influence the canonical Wnt signaling pathway in processes like mesoderm differentiation and tissue stiffness during tumorigenesis, but a molecular mechanism involving both in a developing epithelium and its homeostasis is lacking. We identified that increased non-muscle myosin II activation and cellular contraction inhibited Wnt target gene transcription in developing Drosophila. Genetic interactions studies identified this effect was due to myosin-induced accumulation of cortical F-actin resulting in clustering and accumulation of E-cadherin to the adherens junctions. E-cadherin titrates any available β-catenin, the Wnt pathway transcriptional co-activator, to the adherens junctions in order to maintain cell-cell adhesion under contraction. We show that decreased levels of cytoplasmic β-catenin result in insufficient nuclear translocation for full Wnt target gene transcription. Our work elucidates a mechanism in which the dynamic activation of actomyosin contractility refines patterning of Wnt transcription during development and maintenance of epithelial tissue in organisms.

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