Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

E-cadherin junctions as active mechanical integrators in tissue dynamics

Abstract

During epithelial morphogenesis, E-cadherin adhesive junctions play an important part in mechanically coupling the contractile cortices of cells together, thereby distributing the stresses that drive cell rearrangements at both local and tissue levels. Here we discuss the concept that cellular contractility and E-cadherin-based adhesion are functionally integrated by biomechanical feedback pathways that operate on molecular, cellular and tissue scales.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Actomyosin at epithelial junctions.
Figure 2: Forces and mechanosensitivity at E-cadherin junctions.
Figure 3: Spatial patterns of contraction underlying apical constriction and cell intercalation.

Similar content being viewed by others

Zixuan Zhao, Xinyi Chen, … Hanry Yu

References

  1. Foty, R. A. & Steinberg, M. S. The differential adhesion hypothesis: a direct evaluation. Dev. Biol. 278, 255–263 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Takeichi, M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251, 1451–1455 (1991).

    Article  CAS  PubMed  Google Scholar 

  3. Guillot, C. & Lecuit, T. Mechanics of epithelial tissue homeostasis and morphogenesis. Science 340, 1185–1189 (2013).

    Article  CAS  PubMed  Google Scholar 

  4. Heisenberg, C. P. & Bellaiche, Y. Forces in tissue morphogenesis and patterning. Cell 153, 948–962 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. Krieg, M. et al. Tensile forces govern germ-layer organization in zebrafish. Nat. Cell Biol. 10, 429–436 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Maitre, J. L. et al. Adhesion functions in cell sorting by mechanically coupling the cortices of adhering cells. Science 338, 253–256 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Lecuit, T. & Lenne, P. F. Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nat. Rev. Mol. Cell Biol. 8, 633–644 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Farhadifar, R., Roper, J. C., Aigouy, B., Eaton, S. & Julicher, F. The influence of cell mechanics, cell-cell interactions, and proliferation on epithelial packing. Curr. Biol. 17, 2095–2104 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Brieher, W. M. & Yap, A. S. Cadherin junctions and their cytoskeleton(s). Curr. Opin. Cell Biol. 25, 39–46 (2013).

    Article  CAS  PubMed  Google Scholar 

  10. Takeichi, M. Dynamic contacts: rearranging adherens junctions to drive epithelial remodelling. Nat. Rev. Mol. Cell Biol. 15, 397–410 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. Lecuit, T., Lenne, P. F. & Munro, E. Force generation, transmission, and integration during cell and tissue morphogenesis. Annu. Rev. Cell Dev. Biol. 27, 157–184 (2011).

    Article  CAS  PubMed  Google Scholar 

  12. Martin, A. C., Gelbart, M., Fernandez-Gonzalez, R., Kaschube, M. & Wieschaus, E. F. Integration of contractile forces during tissue invagination. J. Cell Biol. 188, 735–749 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yonemura, S. Cadherin-actin interactions at adherens junctions. Curr. Opin. Cell Biol. 23, 515–522 (2011).

    Article  CAS  PubMed  Google Scholar 

  14. Founounou, N., Loyer, N. & Le Borgne, R. Septins regulate the contractility of the actomyosin ring to enable adherens junction remodeling during cytokinesis of epithelial cells. Dev. Cell 24, 242–255 (2013).

    Article  CAS  PubMed  Google Scholar 

  15. Guillot, C. & Lecuit, T. Adhesion disengagement uncouples intrinsic and extrinsic forces to drive cytokinesis in epithelial tissues. Dev. Cell 24, 227–241 (2013).

    Article  CAS  PubMed  Google Scholar 

  16. Herszterg, S., Leibfried, A., Bosveld, F., Martin, C. & Bellaiche, Y. Interplay between the dividing cell and its neighbors regulates adherens junction formation during cytokinesis in epithelial tissue. Dev. Cell 24, 256–270 (2013).

    Article  CAS  PubMed  Google Scholar 

  17. Morais-de-Sa, E. & Sunkel, C. Adherens junctions determine the apical position of the midbody during follicular epithelial cell division. EMBO Rep. 14, 696–703 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Toyama, Y., Peralta, X. G., Wells, A. R., Kiehart, D. P. & Edwards, G. S. Apoptotic force and tissue dynamics during Drosophila embryogenesis. Science 321, 1683–1686 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Muliyil, S., Krishnakumar, P. & Narasimha, M. Spatial, temporal and molecular hierarchies in the link between death, delamination and dorsal closure. Development 138, 3043–3054 (2011).

    Article  CAS  PubMed  Google Scholar 

  20. Wu, S. K. et al. Cortical F-actin stabilization generates apical–lateral patterns of junctional contractility that integrate cells into epithelia. Nat. Cell Biol. 16, 167–178 (2014).

    Article  CAS  PubMed  Google Scholar 

  21. Hogan, C. et al. Characterization of the interface between normal and transformed epithelial cells. Nat. Cell Biol. 11, 460–467 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Eisenhoffer, G. T. et al. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature 484, 546–549 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Marinari, E. et al. Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding. Nature 484, 542–545 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Walck-Shannon, E. & Hardin, J. Cell intercalation from top to bottom. Nat. Rev. Mol. Cell Biol. 15, 34–48 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Aigouy, B. et al. Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell 142, 773–786 (2010).

    Article  CAS  PubMed  Google Scholar 

  26. Bertet, C., Sulak, L. & Lecuit, T. Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429, 667–671 (2004).

    Article  CAS  PubMed  Google Scholar 

  27. Blankenship, J. T., Backovic, S. T., Sanny, J. S., Weitz, O. & Zallen, J. A. Multicellular rosette formation links planar cell polarity to tissue morphogenesis. Dev. Cell 11, 459–470 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. Bosveld, F. et al. Mechanical control of morphogenesis by Fat/Dachsous/Four-jointed planar cell polarity pathway. Science 336, 724–727 (2012).

    Article  CAS  PubMed  Google Scholar 

  29. Nishimura, T., Honda, H. & Takeichi, M. Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell 149, 1084–1097 (2012).

    Article  CAS  PubMed  Google Scholar 

  30. Campinho, P. et al. Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly. Nat. Cell Biol. 15, 1405–1414 (2013).

    Article  CAS  PubMed  Google Scholar 

  31. Gomez, G. A., McLachlan, R. W. & Yap, A. S. Productive tension: force-sensing and homeostasis of cell–cell junctions. Trends Cell Biol. 21, 499–505 (2011).

    Article  CAS  PubMed  Google Scholar 

  32. Delva, E., Tucker, D. K. & Kowalczyk, A. P. The desmosome. Cold Spring Harb. Perspect. Biol. 1, a002543 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Akhmanova, A., Stehbens, S. J. & Yap, A. S. Touch, grasp, deliver and control: functional cross-talk between microtubules and cell adhesions. Traffic 10, 268–274 (2009).

    Article  CAS  PubMed  Google Scholar 

  34. Miyake, Y. et al. Actomyosin tension is required for correct recruitment of adherens junction components and zonula occludens formation. Exp. Cell Res. 312, 1637–1650 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Shewan, A. M. et al. Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell–cell contacts. Mol. Biol. Cell 16, 4531–4532 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Smutny, M. et al. Myosin II isoforms identify distinct functional modules that support integrity of the epithelial zonula adherens. Nat. Cell Biol. 12, 696–702 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rauzi, M., Lenne, P. F. & Lecuit, T. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature 468, 1110–1114 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Roh-Johnson, M. et al. Triggering a cell shape change by exploiting preexisting actomyosin contractions. Science 335, 1232–1235 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Soares e Silva, M. et al. Active multistage coarsening of actin networks driven by myosin motors. Proc. Natl Acad. Sci. USA 108, 9408–9413 (2011).

    Article  PubMed  CAS  Google Scholar 

  40. Murrell, M. P. & Gardel, M. L. F-actin buckling coordinates contractility and severing in a biomimetic actomyosin cortex. Proc. Natl Acad. Sci. USA 109, 20820–20825 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Behrndt, M. et al. Forces driving epithelial spreading in zebrafish gastrulation. Science 338, 257–260 (2012).

    Article  CAS  PubMed  Google Scholar 

  42. Blanchard, G. B., Murugesu, S., Adams, R. J., Martinez-Arias, A. & Gorfinkiel, N. Cytoskeletal dynamics and supracellular organisation of cell shape fluctuations during dorsal closure. Development 137, 2743–2752 (2010).

    Article  CAS  PubMed  Google Scholar 

  43. Martin, A. C., Kaschube, M. & Wieschaus, E. F. Pulsed contractions of an actin–myosin network drive apical constriction. Nature 457, 495–499 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Mayer, M., Depken, M., Bois, J. S., Julicher, F. & Grill, S. W. Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows. Nature 467, 617–621 (2010).

    Article  CAS  PubMed  Google Scholar 

  45. Solon, J., Kaya-Copur, A., Colombelli, J. & Brunner, D. Pulsed forces timed by a ratchet-like mechanism drive directed tissue movement during dorsal closure. Cell 137, 1331–1342 (2009).

    Article  PubMed  Google Scholar 

  46. Levayer, R. & Lecuit, T. Oscillation and polarity of E-cadherin asymmetries control actomyosin flow patterns during morphogenesis. Dev. Cell 26, 162–175 (2013).

    Article  CAS  PubMed  Google Scholar 

  47. Desai, R. et al. Monomeric α-catenin links cadherin to the actin cytoskeleton. Nat. Cell Biol. 15, 261–273 (2013).

    Article  CAS  PubMed  Google Scholar 

  48. Yonemura, S., Wada, Y., Watanabe, T., Nagafuchi, A. & Shibata, M. α-Catenin as a tension transducer that induces adherens junction development. Nat. Cell Biol. 12, 533–542 (2010).

    Article  CAS  PubMed  Google Scholar 

  49. Rimm, D. L., Koslov, E. R., Kebriaei, P., Cianci, C. D. & Morrow, J. S. a1(E)-Catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. Proc. Natl Acad. Sci. USA 92, 8813–8817 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Watabe-Uchida, M. et al. α-Catenin–vinculin interaction functions to organize the apical junctional complex in epithelial cells. J. Cell Biol. 142, 847–857 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Huveneers, S. et al. Vinculin associates with endothelial VE-cadherin junctions to control force-dependent remodeling. J. Cell Biol. 196, 641–652 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Abe, K. & Takeichi, M. EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes the circumferential actin belt. Proc. Natl Acad. Sci. USA 105, 13–19 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Mangold, S., Norwood, S. J., Yap, A. S. & Collins, B. M. The juxtamembrane domain of the E-cadherin cytoplasmic tail contributes to its interaction with myosin VI. BioArchitecture 2, 185–188 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Maddugoda, M. P., Crampton, M. S., Shewan, A. M. & Yap, A. S. Myosin VI and vinculin cooperate during the morphogenesis of cadherin cell–cell contacts in mammalian epithelial cells. J. Cell Biol. 178, 529–540 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chuan, P., Spudich, J. A. & Dunn, A. R. Robust mechanosensing and tension generation by myosin VI. J. Mol. Biol. 405, 105–112 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Kovacs, E. M. et al. N-WASP regulates the epithelial junctional actin cytoskeleton through a non-canonical post-nucleation pathway. Nat. Cell Biol. 13, 934–943 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Cavey, M., Rauzi, M., Lenne, P. F. & Lecuit, T. A two-tiered mechanism for stabilization and immobilization of E-cadherin. Nature 453, 751–756 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Zhang, J. et al. Actin at cell–cell junctions is composed of two dynamic and functional populations. J. Cell Sci. 118, 5549–5562 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Yonemura, S., Hirao-Minakuchi, K. & Nishimura, Y. Rho localization in cells and tissues. Exp. Cell Res. 295, 300–314 (2004).

    Article  CAS  PubMed  Google Scholar 

  60. Ratheesh, A. et al. Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens. Nat. Cell Biol. 14, 818–828 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Nishimura, T. & Takeichi, M. Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling. Development 135, 1493–1502 (2008).

    Article  CAS  PubMed  Google Scholar 

  62. Smith, A. L., Dohn, M. R., Brown, M. V. & Reynolds, A. B. Association of Rho-associated protein kinase 1 with E-cadherin complexes is mediated by p120-catenin. Mol. Biol. Cell 23, 99–110 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Simoes Sde, M., Mainieri, A. & Zallen, J. A. Rho GTPase and Shroom direct planar polarized actomyosin contractility during convergent extension. J. Cell Biol. 204, 575–589 (2014).

    Article  PubMed  CAS  Google Scholar 

  64. Kovacs, E. M., Ali, R. G., McCormack, A. J. & Yap, A. S. E-cadherin homophilic ligation directly signals through Rac and PI3-kinase to regulate adhesive contacts. J. Biol. Chem. 277, 6708–6718 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Carramusa, L., Ballestrem, C., Zilberman, Y. & Bershadsky, A. D. Mammalian diaphanous-related formin Dia1 controls the organization of E-cadherin-mediated cell–cell junctions. J. Cell Sci. 120, 3870–3882 (2007).

    Article  CAS  PubMed  Google Scholar 

  66. Tang, V. W. & Brieher, W. M. FSGS3/CD2AP is a barbed-end capping protein that stabilizes actin and strengthens adherens junctions. J. Cell Biol. 203, 815–833 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Han, S. P. et al. Cortactin scaffolds Arp2/3 and WAVE2 at the epithelial zonula adherens. J. Biol. Chem. 289, 7764–7775 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Nandadasa, S., Tao, Q., Menon, N. R., Heasman, J. & Wylie, C. N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements. Development 136, 1327–1338 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Koenderink, G. H. et al. An active biopolymer network controlled by molecular motors. Proc. Natl Acad. Sci. USA 106, 15192–15197 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kim, T., Gardel, M. L. & Munro, E. Determinants of fluidlike behavior and effective viscosity in cross-linked actin networks. Biophys. J. 106, 526–534 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Marchetti, M. C. et al. Hydrodynamics of soft active matter. Rev. Mod. Phys. 85, 1143 (2013).

    Article  CAS  Google Scholar 

  72. Joanny, J. F. & Prost, J. Active gels as a description of the actin–myosin cytoskeleton. HFSP J. 3, 94–104 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Rauzi, M., Verant, P., Lecuit, T. & Lenne, P. F. Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis. Nat. Cell Biol. 10, 1401–1410 (2008).

    Article  CAS  PubMed  Google Scholar 

  74. Fernandez-Gonzalez, R., Simoes Sde, M., Roper, J. C., Eaton, S. & Zallen, J. A. Myosin II dynamics are regulated by tension in intercalating cells. Dev. Cell 17, 736–743 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bambardekar, K., Clement, R., Blanc, O., Chardes, C. & Lenne, P. F. Direct laser manipulation reveals the mechanics of cell contacts in vivo. Proc. Natl Acad. Sci. USA 112, 1416–1421 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sherrard, K., Robin, F., Lemaire, P. & Munro, E. Sequential activation of apical and basolateral contractility drives ascidian endoderm invagination. Curr. Biol. 20, 1499–1510 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Dembo, M., Torney, D. C., Saxman, K. & Hammer, D. The reaction-limited kinetics of membrane-to-surface adhesion and detachment. Proc. R. Soc. Lond. B Biol. Sci. 234, 55–83 (1988).

    Article  CAS  PubMed  Google Scholar 

  78. Rakshit, S. & Sivasankar, S. Biomechanics of cell adhesion: how force regulates the lifetime of adhesive bonds at the single molecule level. Phys. Chem. Chem. Phys. 16, 2211–2223 (2014).

    Article  CAS  PubMed  Google Scholar 

  79. Harrison, O. J. et al. Two-step adhesive binding by classical cadherins. Nat. Struct. Mol. Biol. 17, 348–357 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Rakshit, S., Zhang, Y., Manibog, K., Shafraz, O. & Sivasankar, S. Ideal, catch, and slip bonds in cadherin adhesion. Proc. Natl Acad. Sci. USA 109, 18815–18820 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Manibog, K., Li, H., Rakshit, S. & Sivasankar, S. Resolving the molecular mechanism of cadherin catch bond formation. Nat. Commun. 5, 3941 (2014).

    Article  CAS  PubMed  Google Scholar 

  82. Wu, Y., Kanchanawong, P. & Zaidel-Bar, R. Actin-delimited adhesion-independent clustering of E-cadherin forms the nanoscale building blocks of adherens junctions. Dev. Cell 32, 139–154 (2015).

    Article  CAS  PubMed  Google Scholar 

  83. Yap, A. S., Brieher, W. M., Pruschy, M. & Gumbiner, B. M. Lateral clustering of the adhesive ectodomain: a fundamental determinant of cadherin function. Curr. Biol. 7, 308–315 (1997).

    Article  CAS  PubMed  Google Scholar 

  84. Angres, B., Barth, A. & Nelson, W. J. Mechanism for transition from initial to stable cell–cell adhesion: kinetic analysis of E-cadherin-mediated adhesion using a quantitative adhesion assay. J. Cell Biol. 134, 549–557 (1996).

    Article  CAS  PubMed  Google Scholar 

  85. Truong Quang, B. A., Mani, M., Markova, O., Lecuit, T. & Lenne, P. F. Principles of E-cadherin supramolecular organization in vivo. Curr. Biol. 23, 2197–2207 (2013).

    Article  CAS  PubMed  Google Scholar 

  86. Engl, W., Arasi, B., Yap, L. L., Thiery, J. P. & Viasnoff, V. Actin dynamics modulate mechanosensitive immobilization of E-cadherin at adherens junctions. Nat. Cell Biol. 16, 587–594 (2014).

    Article  CAS  PubMed  Google Scholar 

  87. Priya, R., Yap, A. S. & Gomez, G. A. E-cadherin supports steady-state Rho signaling at the epithelial zonula adherens. Differentiation 86, 133–140 (2013).

    Article  CAS  PubMed  Google Scholar 

  88. le Duc, Q. et al. Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J. Cell Biol. 189, 1107–1115 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Barry, A. K. et al. α-Catenin cytomechanics—role in cadherin-dependent adhesion and mechanotransduction. J. Cell Sci. 127, 1779–1791 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Leerberg, J. M. et al. Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens. Curr. Biol. 24, 1689–1699 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Drees, F., Pokutta, S., Yamada, S., Nelson, W. J. & Weis, W. I. α-Catenin is a molecular switch that binds E-cadherin-β-catenin and regulates actin-filament assembly. Cell 123, 903–915 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Buckley, C. D. et al. The minimal cadherin-catenin complex binds to actin filaments under force. Science 346, 1254211 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. De la Cruz, E. M. & Ostap, E. M. Relating biochemistry and function in the myosin superfamily. Curr. Op. Cell Biol. 16, 61–67 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. West-Foyle, H. & Robinson, D. N. Cytokinesis mechanics and mechanosensing. Cytoskeleton (Hoboken) 69, 700–709 (2012).

    Article  Google Scholar 

  95. Yonemura, S., Wada, Y., Watanabe, T., Nagafuchi, A. & Shibata, M. α-Catenin as a tension transducer that induces adherens junction development. Nat. Cell Biol. 12, 533–542 (2010).

    Article  CAS  PubMed  Google Scholar 

  96. Norstrom, M. F., Smithback, P. A. & Rock, R. S. Unconventional processive mechanics of non-muscle myosin IIB. J. Biol. Chem. 285, 26326–26334 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hansen, S. D. & Mullins, R. D. VASP is a processive actin polymerase that requires monomeric actin for barbed end association. J. Cell Biol. 191, 571–584 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Bear, J. E. et al. Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility. Cell 109, 509–521 (2002).

    Article  CAS  PubMed  Google Scholar 

  99. Yao, M. et al. Force-dependent conformational switch of α-catenin controls vinculin binding. Nat. Commun. 5, 4525 (2014).

    Article  CAS  PubMed  Google Scholar 

  100. Borghi, N. et al. E-cadherin is under constitutive actomyosin-generated tension that is increased at cell–cell contacts upon externally applied stretch. Proc. Natl Acad. Sci. USA 109, 12568–12573 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Conway, D. E. et al. Fluid shear stress on endothelial cells modulates mechanical tension across VE-cadherin and PECAM-1. Curr. Biol. 23, 1024–1030 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Tzima, E. et al. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437, 426–431 (2005).

    Article  CAS  PubMed  Google Scholar 

  103. Noren, N. K., Niessen, C. M., Gumbiner, B. M. & Burridge, K. Cadherin engagement regulates Rho family GTPases. J. Biol. Chem. 276, 33305–33308 (2001).

    Article  CAS  PubMed  Google Scholar 

  104. Hogan, C. et al. Rap1 regulates the formation of E-cadherin-based cell–cell contacts. Mol. Cell Biol. 24, 6690–6700 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. McLachlan, R. W., Kraemer, A., Helwani, F. M., Kovacs, E. M. & Yap, A. S. E-cadherin adhesion activates c-Src signaling at cell–cell contacts. Mol. Biol. Cell 18, 3214–3223 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Pece, S., Chiariello, M., Murga, C. & Gutkind, J. S. Activation of the protein kinase Akt/PKB by the formation of E-cadherin-mediated cell–cell junctions. J. Biol. Chem. 274, 19347–19351 (1999).

    Article  CAS  PubMed  Google Scholar 

  107. Martin, A. C. & Goldstein, B. Apical constriction: themes and variations on a cellular mechanism driving morphogenesis. Development 141, 1987–1998 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Dawes-Hoang, R. E. et al. Folded gastrulation, cell shape change and the control of myosin localization. Development 132, 4165–4178 (2005).

    Article  CAS  PubMed  Google Scholar 

  109. Mason, F. M., Tworoger, M. & Martin, A. C. Apical domain polarization localizes actin–myosin activity to drive ratchet-like apical constriction. Nat. Cell Biol. 15, 926–936 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Bolinger, C., Zasadil, L., Rizaldy, R. & Hildebrand, J. D. Specific isoforms of Drosophila shroom define spatial requirements for the induction of apical constriction. Dev. Dyn. 239, 2078–2093 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Haigo, S. L., Hildebrand, J. D., Harland, R. M. & Wallingford, J. B. Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr. Biol. 13, 2125–2137 (2003).

    Article  CAS  PubMed  Google Scholar 

  112. Hildebrand, J. D. Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. J. Cell Sci. 118, 5191–5203 (2005).

    Article  CAS  PubMed  Google Scholar 

  113. Voiculescu, O., Bertocchini, F., Wolpert, L., Keller, R. E. & Stern, C. D. The amniote primitive streak is defined by epithelial cell intercalation before gastrulation. Nature 449, 1049–1052 (2007).

    Article  CAS  PubMed  Google Scholar 

  114. Trichas, G. et al. Multi-cellular rosettes in the mouse visceral endoderm facilitate the ordered migration of anterior visceral endoderm cells. PLoS Biol. 10, e1001256 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Shindo, A. & Wallingford, J. B. PCP and septins compartmentalize cortical actomyosin to direct collective cell movement. Science 343, 649–652 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Simoes Sde, M. et al. Rho-kinase directs Bazooka/Par-3 planar polarity during Drosophila axis elongation. Dev. Cell 19, 377–388 (2010).

    Article  PubMed  CAS  Google Scholar 

  117. Levayer, R., Pelissier-Monier, A. & Lecuit, T. Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis. Nat. Cell Biol. 13, 529–540 (2011).

    Article  CAS  PubMed  Google Scholar 

  118. Cai, D. & Montell, D. J. Diverse and dynamic sources and sinks in gradient formation and directed migration. Curr. Opin. Cell Biol. 30C, 91–98 (2014).

    Article  CAS  Google Scholar 

  119. Cai, Y. et al. Cytoskeletal coherence requires myosin-IIA contractility. J. Cell Sci. 123, 413–423 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

T.L. was funded by Labex INFORM (ANR-11-LABX-0054) under the A*MIDEX program (ANR-11-IDEX-0001-02), the Agence Nationale de la Recherche (Programme Blance 'Archiplast'), the European Research Council (Biomecamorph #323027) and the Association pour la Recherche sur le Cancer (grant SL220120605305). A.S.Y. was funded by the National Health and Medical Research Council of Australia (1044041, 1037320).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Thomas Lecuit or Alpha S. Yap.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lecuit, T., Yap, A. E-cadherin junctions as active mechanical integrators in tissue dynamics. Nat Cell Biol 17, 533–539 (2015). https://doi.org/10.1038/ncb3136

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb3136

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing