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:

The interplay between cell signalling and mechanics in developmental processes

Nature Reviews Genetics volume 14, pages 733–744 (2013)Cite this article

Subjects

Key Points

  • Spatial, temporal and mechanical cues control gene expression and protein activity that regulate force production and mechanical tissue responses in embryos. It is not well understood how mechanical cues determine cell fate or alter gene expression.

  • Various experiments have aimed to understand the role of mechanically activated cell signalling during morphogenesis. Molecular and genetic manipulations have been used, along with analyses of the spatial and temporal mechanisms that transmit and coordinate forces in the tissue. In vivo and in vitro studies have identified the roles of biomechanical cues in guiding cell fate and behaviour.

  • Recent experiments have shown that cellular mechanosensing is broken down into mechanical signals from the microenvironment of the cell and from the plasma membrane and cell cortex. These signals might alter the activity of transcription factors through cell signalling.

  • Mechanical signals have been shown to have a role in complex and poorly understood feedback loops that underlie the robust programmes of development.

Abstract

Force production and the propagation of stress and strain within embryos and organisms are crucial physical processes that direct morphogenesis. In addition, there is mounting evidence that biomechanical cues created by these processes guide cell behaviours and cell fates. In this Review we discuss key roles for biomechanics during development to directly shape tissues, to provide positional information for cell fate decisions and to enable robust programmes of development. Several recently identified molecular mechanisms suggest how cells and tissues might coordinate their responses to biomechanical cues. Finally, we outline long-term challenges in integrating biomechanics with genetic analysis of developing embryos.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Forces contributing to tissue movements in development.
Figure 2: Information flow and molecular origins of mechanics.
Figure 3: Mechanical feedback during morphogenesis.

Similar content being viewed by others

References

  1. His, W. On the principles of animal morphology. Proc. R. Soc. Edinburgh 15, 287–298 (1888).

    Google Scholar 

  2. Rhumbler, L. Zur mechanik des gastrulationsvorganges insbesondere der invagination. Archiv für Entwicklungsmechanik der Organismen 14, 401–476 (1902) (in German).

    Article  Google Scholar 

  3. Morgan, T. H. Experimental Embryology (Columbia Univ. Press, 1927).

    Book  Google Scholar 

  4. Lewis, W. H. Mechanics of Invagination. Anatom. Record 97, 139–156 (1947).

    Article  CAS  Google Scholar 

  5. Howard, J. Mechanics of Motor Proteins and the Cytoskeleton (Sinauer Associates, 2001).

    Google Scholar 

  6. Selman, G. G. Studies on the forces producing neural closure in amphibia. Proc. R. Phys. Soc. Edinburgh 24, 24–27 (1955).

    Google Scholar 

  7. Selman, G. G. The forces producing neural closure in amphibia. J. Embryol. Exp. Morphol. 6, 448–465 (1958).

    CAS  PubMed  Google Scholar 

  8. Smith, J. L. & Schoenwolf, G. C. Further evidence of extrinsic forces in bending of the neural plate. J. Comp. Neurol. 307, 225–236 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Alvarez, I. S. & Schoenwolf, G. C. Expansion of surface epithelium provides the major extrinsic force for bending of the neural plate. J. Exp. Zool. 261, 340–348 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Smith, J. L., Schoenwolf, G. C. & Quan, J. Quantitative analyses of neuroepithelial cell shapes during bending of the mouse neural plate. J. Comp. Neurol. 342, 144–151 (1994).

    Article  CAS  PubMed  Google Scholar 

  11. Smith, J. L. & Schoenwolf, G. C. Neurulation: coming to closure. Trends Neurosci. 20, 510–517 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Ettensohn, C. A. Mechanisms of epithelial invagination. Quarterly Rev. Biol. 60, 289–307 (1985).

    Article  CAS  Google Scholar 

  13. Gustafson, T. & Wolpert, L. The cellular basis of morphogenesis and sea urchin development. Int. Rev. Cytol. 15, 139–214 (1963).

    Article  CAS  PubMed  Google Scholar 

  14. Moore, A. R. & Burt, A. S. On the locus and nature of the forces causing gastrulation in the embryos of Dendraster excentricus. J. Exp. Zool. 82, 159–171 (1939).

    Article  Google Scholar 

  15. Hutson, M. S. et al. Forces for morphogenesis investigated with laser microsurgery and quantitative modeling. Science 300, 145–149 (2003). This article described the mechanical steps required for D. melanogaster dorsal closure. The authors used laser ablation to describe the direction and relative magnitude of stress and test contribution of forces from different tissues.

    Article  CAS  PubMed  Google Scholar 

  16. Peralta, X. G. et al. Upregulation of forces and morphogenic asymmetries in dorsal closure during Drosophila development. Biophys. J. 92, 2583–2596 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 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 

  18. Kiehart, D. P., Galbraith, C. G., Edwards, K. A., Rickoll, W. L. & Montague, R. A. Multiple forces contribute to cell sheet morphogenesis for dorsal closure in Drosophila. J. Cell Biol. 149, 471–490 (2000). These authors examined the forces responsible for dorsal closure in D. melanogaster using three techniques: time-lapse confocal microscopy of actomyosin dynamics, laser cutting and repeated ablation of cells. These techniques were used to test the relative contribution of distinct morphogenetic 'motors' to dorsal closure.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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 

  20. Gorfinkiel, N., Blanchard, G. B., Adams, R. J. & Martinez Arias, A. Mechanical control of global cell behaviour during dorsal closure in Drosophila. Development 136, 1889–1898 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. David, D. J., Tishkina, A. & Harris, T. J. The PAR complex regulates pulsed actomyosin contractions during amnioserosa apical constriction in Drosophila. Development 137, 1645–1655 (2010).

    Article  CAS  PubMed  Google Scholar 

  22. Young, P. E., Richman, A. M., Ketchum, A. S. & Kiehart, D. P. Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function. Genes Dev. 7, 29–41 (1993).

    Article  CAS  PubMed  Google Scholar 

  23. Edwards, K. A., Demsky, M., Montague, R. A., Weymouth, N. & Kiehart, D. P. GFP-moesin illuminates actin cytoskeleton dynamics in living tissue and demonstrates cell shape changes during morphogenesis in Drosophila. Dev. Biol. 191, 103–117 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Jacinto, A. et al. Dynamic analysis of actin cable function during Drosophila dorsal closure. Curr. Biol. 12, 1245–1250 (2002).

    Article  CAS  PubMed  Google Scholar 

  25. Millard, T. H. & Martin, P. Dynamic analysis of filopodial interactions during the zippering phase of Drosophila dorsal closure. Development 135, 621–626 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Davidson, L. A., Koehl, M. A., Keller, R. & Oster, G. F. How do sea urchins invaginate? Using biomechanics to distinguish between mechanisms of primary invagination. Development 121, 2005–2018 (1995). This study used finite element modelling to test hypothesized mechanisms for sea urchin primary invagination and applied the model results to develop experiments that would ascertain the in vivo mechanism.

    Article  CAS  PubMed  Google Scholar 

  27. Davidson, L. A., Oster, G. F., Keller, R. E. & Koehl, M. A. Measurements of mechanical properties of the blastula wall reveal which hypothesized mechanisms of primary invagination are physically plausible in the sea urchin Strongylocentrotus purpuratus. Dev. Biol. 209, 221–238 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. 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 

  29. Koehl, M. A. R. Biomechanical approaches to morphogenesis. Seminars Dev. Biol. 1, 367–378 (1990).

    Google Scholar 

  30. Trinkaus, J. P. Cells Into Organs: The Forces That Shape The Embryo (Prentice-Hall, 1984).

    Google Scholar 

  31. Harris, A. K., Wild, P. & Stopak, D. Silicone rubber substrata: a new wrinkle in the study of cell locomotion. Science 208, 177–179 (1980).

    Article  CAS  PubMed  Google Scholar 

  32. Dembo, M. & Wang, Y. L. Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys. J. 76, 2307–2316 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang, H. B., Dembo, M., Hanks, S. K. & Wang, Y. Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc. Natl Acad. Sci. USA 98, 11295–11300 (2001). This study examined the role of focal adhesion kinase in mechanosensing. The researchers applied forces by pulling or pushing the substrate near the cell with a microneedle.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chen, C. S., Mrksich, M., Huang, S., Whitesides, G. M. & Ingber, D. E. Geometric control of cell life and death. Science 276, 1425–1428 (1997).

    Article  CAS  PubMed  Google Scholar 

  35. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006). Here, the authors tuned the elasticity of in vitro gels to physiological elasticity and observed the corresponding differentiation of human mesenchymal stem cells.

    Article  CAS  PubMed  Google Scholar 

  36. Trappmann, B. et al. Extracellular-matrix tethering regulates stem-cell fate. Nature Mater. 11, 642–649 (2012).

    Article  CAS  Google Scholar 

  37. McBeath, R., Pirone, D. M., Nelson, C. M., Bhadriraju, K. & Chen, C. S. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6, 483–495 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Brodland, G. W. et al. Furrowing surface contraction wave coincident with primary neural induction in amphibian embryos. J. Morphol. 219, 131–142 (1994).

    Article  CAS  PubMed  Google Scholar 

  39. Beloussov, L. V., Lakirev, A. V., Naumidi, I. I. & Novoselov, V. V. Effects of relaxation of mechanical tensions upon the early morphogenesis of Xenopus laevis embryos. Int. J. Dev. Biol. 34, 409–419 (1990).

    CAS  PubMed  Google Scholar 

  40. Beloussov, L. V., Luchinskaya, N. N., Ermakov, A. S. & Glagoleva, N. S. Gastrulation in amphibian embryos, regarded as a succession of biomechanical feedback events. Int. J. Dev. Biol. 50, 113–122 (2006).

    Article  PubMed  Google Scholar 

  41. Desprat, N., Supatto, W., Pouille, P. A., Beaurepaire, E. & Farge, E. Tissue deformation modulates twist expression to determine anterior midgut differentiation in Drosophila embryos. Dev. Cell 15, 470–477 (2008). These authors used laser ablation and magnetic tweezers to deform D. melanogaster embryos and draw conclusions about mechanically induced factors.

    Article  CAS  PubMed  Google Scholar 

  42. Farge, E. Mechanical induction of Twist in the Drosophila foregut/stomodeal primordium. Curr. Biol. 13, 1365–1377 (2003). In this study, compression was applied to deform D. melanogaster embryos, and the authors observed the transcription patterns of multiple genes after compression.

    Article  CAS  PubMed  Google Scholar 

  43. Kumar, A. & Shivashankar, G. Mechanical force alters morphogenetic movements and segmental gene expression patterns during Drosophila embryogenesis. PLoS ONE 7, e33089 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 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 

  45. Keller, R., Davidson, L. A. & Shook, D. R. How we are shaped: the biomechanics of gastrulation. Differentiation 71, 171–205 (2003).

    Article  PubMed  Google Scholar 

  46. Sampath, K. et al. Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling. Nature 395, 185–189 (1998).

    Article  CAS  PubMed  Google Scholar 

  47. Pouille, P. A., Ahmadi, P., Brunet, A. C. & Farge, E. Mechanical signals trigger Myosin II redistribution and mesoderm invagination in Drosophila embryos. Sci. Signal 2, ra16 (2009).

    Article  PubMed  CAS  Google Scholar 

  48. Martin, A. C., Kaschube, M. & Wieschaus, E. F. Pulsed contractions of an actin-myosin network drive apical constriction. Nature 457, 495–499 (2009). This study elucidated that apical constriction of ventral furrow cells in Drosophila melanogaster is caused by pulsed actomyosin contractions.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  50. Somogyi, K. & Rorth, P. Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration. Dev. Cell 7, 85–93 (2004).

    Article  CAS  PubMed  Google Scholar 

  51. Garcia, A. J., Vega, M. D. & Boettiger, D. Modulation of cell proliferation and differentiation through substrate-dependent changes in fibronectin conformation. Mol. Biol. Cell 10, 785–798 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Krammer, A., Lu, H., Isralewitz, B., Schulten, K. & Vogel, V. Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch. Proc. Natl Acad. Sci. USA 96, 1351–1356 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Klotzsch, E. et al. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites. Proc. Natl Acad. Sci. USA 106, 18267–18272 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Baneyx, G., Baugh, L. & Vogel, V. Fibronectin extension and unfolding within cell matrix fibrils controlled by cytoskeletal tension. Proc. Natl Acad. Sci. USA 99, 5139–5143 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Marsden, M. & DeSimone, D. W. Regulation of cell polarity, radial intercalation and epiboly in Xenopus: novel roles for integrin and fibronectin. Development 128, 3635–3647 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Davidson, L. A., Marsden, M., Keller, R. & Desimone, D. W. Integrin α5β1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension. Curr. Biol. 16, 833–844 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Trinh, L. A. & Stainier, D. Y. Fibronectin regulates epithelial organization during myocardial migration in zebrafish. Dev. Cell 6, 371–382 (2004).

    Article  CAS  PubMed  Google Scholar 

  58. Chiu, C. H., Chou, C. W., Takada, S. & Liu, Y. W. Development and fibronectin signaling requirements of the zebrafish interrenal vessel. PLoS ONE 7, e43040 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Pulina, M. V. et al. Essential roles of fibronectin in the development of the left-right embryonic body plan. Dev. Biol. 354, 208–220 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Weber, G. F., Bjerke, M. A. & Desimone, D. W. A mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration. Dev. Cell 22, 104–115 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Raich, W. B., Agbunag, C. & Hardin, J. Rapid epithelial-sheet sealing in the Caenorhabditis elegans embryo requires cadherin-dependent filopodial priming. Curr. Biol. 9, 1139–1146 (1999).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  63. Kong, F. et al. Cyclic mechanical reinforcement of integrin-ligand interactions. Mol. Cell 49, 1060–1068 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Xu, W., Baribault, H. & Adamson, E. D. Vinculin knockout results in heart and brain defects during embryonic development. Development 125, 327–337 (1998).

    Article  CAS  PubMed  Google Scholar 

  65. 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 

  66. Mierke, C. T. et al. Mechano-coupling and regulation of contractility by the vinculin tail domain. Biophys. J. 94, 661–670 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. del Rio, A. et al. Stretching single talin rod molecules activates vinculin binding. Science 323, 638–641 (2009).

    Article  CAS  PubMed  Google Scholar 

  68. Ho, T. C., Horn, N. A., Huynh, T., Kelava, L. & Lansman, J. B. Evidence TRPV4 contributes to mechanosensitive ion channels in mouse skeletal muscle fibers. Channels (Austin) 6, 246–254 (2012).

    Article  CAS  Google Scholar 

  69. Thodeti, C. K. et al. TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling. Circ. Res. 104, 1123–1130 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kottgen, M. et al. TRPP2 and TRPV4 form a polymodal sensory channel complex. J. Cell Biol. 182, 437–447 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Cosens, D. J. & Manning, A. Abnormal electroretinogram from a Drosophila mutant. Nature 224, 285–287 (1969).

    Article  CAS  PubMed  Google Scholar 

  72. Liedtke, W., Tobin, D. M., Bargmann, C. I. & Friedman, J. M. Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 100, 14531–14536 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Coste, B. et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483, 176–181 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kim, S. E., Coste, B., Chadha, A., Cook, B. & Patapoutian, A. The role of Drosophila Piezo in mechanical nociception. Nature 483, 209–212 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 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 

  76. Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Houk, A. R. et al. Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration. Cell 148, 175–188 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Itoh, T. et al. Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins. Dev. Cell 9, 791–804 (2005).

    Article  CAS  PubMed  Google Scholar 

  79. Suetsugu, S. The proposed functions of membrane curvatures mediated by the BAR domain superfamily proteins. J. Biochem. 148, 1–12 (2010).

    Article  CAS  PubMed  Google Scholar 

  80. Saarikangas, J. et al. Molecular mechanisms of membrane deformation by I-BAR domain proteins. Curr. Biol. 19, 95–107 (2009).

    Article  CAS  PubMed  Google Scholar 

  81. Schuler, S. et al. Ciliated sensory hair cell formation and function require the F-BAR protein syndapin I and the WH2 domain-based actin nucleator Cobl. J. Cell Sci. 126(Pt 1),196–208 (2013).

    Article  PubMed  CAS  Google Scholar 

  82. Parmar, K. M. et al. Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J. Clin. Invest. 116, 49–58 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Lee, J. S. et al. Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Dev. Cell 11, 845–857 (2006).

    Article  CAS  PubMed  Google Scholar 

  84. Groenendijk, B. C., Hierck, B. P., Gittenberger-De Groot, A. C. & Poelmann, R. E. Development-related changes in the expression of shear stress responsive genes KLF-2, ET-1, and NOS-3 in the developing cardiovascular system of chicken embryos. Dev. Dyn. 230, 57–68 (2004).

    Article  CAS  PubMed  Google Scholar 

  85. Wang, N. et al. Shear stress regulation of Kruppel-like factor 2 expression is flow pattern-specific. Biochem. Biophys. Res. Commun. 341, 1244–1251 (2006).

    Article  CAS  PubMed  Google Scholar 

  86. Dupont, S. et al. Role of YAP/TAZ in mechanotransduction. Nature 474, 179–183 (2011).

    Article  CAS  PubMed  Google Scholar 

  87. Gee, S. T., Milgram, S. L., Kramer, K. L., Conlon, F. L. & Moody, S. A. Yes-associated protein 65 (YAP) expands neural progenitors and regulates Pax3 expression in the neural plate border zone. PLoS ONE 6, e20309 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Morin-Kensicki, E. M. et al. Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Mol. Cell. Biol. 26, 77–87 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sandmann, T. et al. A core transcriptional network for early mesoderm development in Drosophila melanogaster. Genes Dev. 21, 436–449 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Pearson, R., Fleetwood, J., Eaton, S., Crossley, M. & Bao, S. Krüppel-like transcription factors: a functional family. Int. J. Biochem. Cell Biol. 40, 1996–2001 (2008).

    Article  CAS  PubMed  Google Scholar 

  91. Fu, J. et al. Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nature Methods 7, 733–736 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Manu et al. Canalization of gene expression in the Drosophila blastoderm by gap gene cross regulation. PLoS Biol. 7, e1000049 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Tyszka, J. M., Ewald, A. J., Wallingford, J. B. & Fraser, S. E. New tools for visualization and analysis of morphogenesis in spherical embryos. Dev. Dyn. 234, 974–983 (2005).

    Article  PubMed  Google Scholar 

  94. Jiang, X., Bruzewicz, D. A., Wong, A. P., Piel, M. & Whitesides, G. M. Directing cell migration with asymmetric micropatterns. Proc. Natl Acad. Sci. USA 102, 975–978 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. von Dassow, M. & Davidson, L. A. Physics and the canalization of morphogenesis: a grand challenge in organismal biology. Phys. Biol. 8, 045002 (2011). These authors used simple in vivo mechanical experiments and theoretical models to describe the viscoelastic properties of a vertebrate embryo and to rule out the presence of mechanical feedback in X. laevis embryonic tissues.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Farge, E. Mechanotransduction in development. Curr. Top. Dev. Biol. 95, 243–265 (2011).

    Article  PubMed  Google Scholar 

  97. Shook, D. R. & Keller, R. Morphogenic machines evolve more rapidly than the signals that pattern them: lessons from amphibians. J. Exp. Zool. B Mol. Dev. Evol. 310, 111–135 (2008).

    Article  PubMed  Google Scholar 

  98. 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 

  99. Sweeney, H. L. & Houdusse, A. Structural and functional insights into the Myosin motor mechanism. Annu. Rev. Biophys. 39, 539–557 (2010).

    Article  CAS  PubMed  Google Scholar 

  100. von Dassow, M., Strother, J. A. & Davidson, L. A. Surprisingly simple mechanical behavior from a complex embryonic tissue. PLoS ONE 5, e15359 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Ma, X., Lynch, H. E., Scully, P. C. & Hutson, M. S. Probing embryonic tissue mechanics with laser hole drilling. Phys. Biol. 6, 036004 (2009).

    Article  PubMed  CAS  Google Scholar 

  102. Rodriguez-Diaz, A. et al. Actomyosin purse strings: renewable resources that make morphogenesis robust and resilient. HFSP J. 2, 220–237 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Benazeraf, B. et al. A random cell motility gradient downstream of FGF controls elongation of an amniote embryo. Nature 466, 248–252 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Varner, V. D., Voronov, D. A. & Taber, L. A. Mechanics of head fold formation: investigating tissue-level forces during early development. Development 137, 3801–3811 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  105. Beloussov, L. V., Lakirev, A. V. & Naumidi, I. I. The role of external tensions in differentiation of Xenopus laevis embryonic tissues. Cell Differ. Dev. 25, 165–176 (1988).

    Article  CAS  PubMed  Google Scholar 

  106. Beloussov, L. V., Dorfman, J. G. & Cherdantzev, V. G. Mechanical stresses and morphological patterns in amphibian embryos. J. Embryol. Exp. Morphol. 34, 559–574 (1975).

    CAS  PubMed  Google Scholar 

  107. Sokolow, A., Toyama, Y., Kiehart, D. P. & Edwards, G. S. Cell ingression and apical shape oscillations during dorsal closure in Drosophila. Biophys. J. 102, 969–979 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Peralta, X. G., Toyama, Y., Kiehart, D. P. & Edwards, G. S. Emergent properties during dorsal closure in Drosophila morphogenesis. Phys. Biol. 5, 15004 (2008).

    Article  CAS  Google Scholar 

  109. Blanchard, G. B. et al. Tissue tectonics: morphogenetic strain rates, cell shape change and intercalation. Nature Methods 6, 458–464 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Gibson, M. C., Patel, A. B., Nagpal, R. & Perrimon, N. The emergence of geometric order in proliferating metazoan epithelia. Nature 442, 1038–1041 (2006).

    Article  CAS  PubMed  Google Scholar 

  111. Zhou, J., Kim, H. Y. & Davidson, L. A. Actomyosin stiffens the vertebrate embryo during crucial stages of elongation and neural tube closure. Development 136, 677–688 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhou, J., Kim, H. Y., Wang, J. H. & Davidson, L. A. Macroscopic stiffening of embryonic tissues via microtubules, RhoGEF and the assembly of contractile bundles of actomyosin. Development 137, 2785–2794 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Wiebe, C. & Brodland, G. W. Tensile properties of embryonic epithelia measured using a novel instrument. J. Biomech. 38, 2087–2094 (2005).

    Article  PubMed  Google Scholar 

  114. Zamir, E. A. & Taber, L. A. Material properties and residual stress in the stage 12 chick heart during cardiac looping. J. Biomech. Eng. 126, 823–830 (2004).

    Article  PubMed  Google Scholar 

  115. Foty, R. A., Pfleger, C. M., Forgacs, G. & Steinberg, M. S. Surface tensions of embryonic tissues predict their mutual envelopment behavior. Development 122, 1611–1620 (1996).

    Article  CAS  PubMed  Google Scholar 

  116. Forgacs, G., Foty, R. A., Shafrir, Y. & Steinberg, M. S. Viscoelastic properties of living embryonic tissues: a quantitative study. Biophys. J. 74, 2227–2234 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Joshi, S. D., von Dassow, M. & Davidson, L. A. Experimental control of excitable embryonic tissues: three stimuli induce rapid epithelial contraction. Exp. Cell Res. 316, 103–114 (2010).

    Article  CAS  PubMed  Google Scholar 

  118. Voronov, D. A. & Taber, L. A. Cardiac looping in experimental conditions: effects of extraembryonic forces. Dev. Dyn. 224, 413–421 (2002).

    Article  PubMed  Google Scholar 

  119. Zamir, E. A., Srinivasan, V., Perucchio, R. & Taber, L. A. Mechanical asymmetry in the embryonic chick heart during looping. Ann. Biomed. Eng. 31, 1327–1336 (2003).

    Article  PubMed  Google Scholar 

  120. Odell, G. M., Oster, G., Alberch, P. & Burnside, B. The mechanical basis of morphogenesis. I. Epithelial folding and invagination. Dev. Biol. 85, 446–462 (1981).

    Article  CAS  PubMed  Google Scholar 

  121. Brodland, G. W. et al. Video force microscopy reveals the mechanics of ventral furrow invagination in Drosophila. Proc. Natl Acad. Sci. USA 107, 22111–22116 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Savin, T. et al. On the growth and form of the gut. Nature 476, 57–62 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Brodland, G. W. & Veldhuis, J. H. Assessing the mechanical energy costs of various tissue reshaping mechanisms. Biomech. Model. Mechanobiol. 11, 1137–1147 (2012).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank members of the Davidson laboratory for their support and ongoing discussions on the role of mechanics in development. This work was supported by the National Science Foundation (IOS-0845775, LAD and CJM) and the US National Institutes of Health (HD044750 and ES019259, L.A.D.; 2T32EB003392, C.J.M.).

Author information

Authors and Affiliations

  1. Bioengineering, University of Pittsburgh, Pittsburgh, 15213, Pennsylvania, USA

    Callie Johnson Miller & Lance A. Davidson

  2. Developmental Biology, University of Pittsburgh, Pittsburgh, 15201, Pennsylvania, USA

    Lance A. Davidson

  3. Computational and Systems Biology, University of Pittsburgh, Pittsburgh, 15213, Pennsylvania, USA

    Lance A. Davidson

Authors
  1. Callie Johnson Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lance A. Davidson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lance A. Davidson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Glossary

Gastrulation

Stage of embryonic development when large cell rearrangements occur and the three germ layers — endoderm, mesoderm and ectoderm — of the embryo are established.

Vegetal plate

The columnar epithelium at the vegetal pole of an echinoderm embryo. The thickened vegetal plate forms a pocket and tube by invagination during gastrulation to form the archenteron, or primitive gut, of the embryo.

Blastula

The early stage of a developing embryo after rapid cell divisions have created a sphere, sometimes hollow, of many cells.

Ectoderm

The outermost germ layer of the embryo. Cells from this layer differentiate into skin and neural tissues.

Dorsal closure

A step in Drosophila melanogaster development in which the epidermis closes over the exposed amnioserosa.

Amnioserosa

A layer of epithelial cells that covers dorsal regions of the early Drosophila melanogaster embryo.

Epidermis

The outermost epithelial layer of an embryo.

Anterior

The axis of the embryo defined by the tissues fated to form the head.

Posterior

The axis of the embryo defined by the tissues fated to form the tail.

Invagination

The 'in-folding' of an epithelium.

Apical

Surfaces that face the 'outside' or lumen.

Basal

Surfaces that face in the opposite direction to apical surfaces; that is, away from the 'outside'.

Traction force microscopy

A method used to determine the force that a cell or tissue exerts on a substrate to which it is adhered.

Focal adhesion complex

A dynamic protein complex that connects the cytoskeleton of the cell to the extracellular matrix.

Desmosomes

A spot-like junctional complex for cell–cell adhesion that is distinct from adherens junctions (which connect epithelial cells to neighbours at their apical ends).

Cell cortex

A layer of cytoplasm just inside the plasma membrane. Cytoskeletal proteins in the cell cortex maintain the shape of the cell.

Stomodeal primordium

A tissue fated to give rise to the Drosophila melanogaster foregut.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miller, C., Davidson, L. The interplay between cell signalling and mechanics in developmental processes. Nat Rev Genet 14, 733–744 (2013). https://doi.org/10.1038/nrg3513

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg3513

This article is cited by

Search

Advanced 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