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.

Cytosystems dynamics in self-organization of tissue architecture

Abstract

Our knowledge of the principles by which organ architecture develops through complex collective cell behaviours is still limited. Recent work has shown that the shape of such complex tissues as the optic cup forms by self-organization in vitro from a homogeneous population of stem cells. Multicellular self-organization involves three basic processes that are crucial for the emergence of latent intrinsic order. Based on lessons from recent studies, cytosystems dynamics is proposed as a strategy for understanding collective multicellular behaviours, incorporating four-dimensional measurement, theoretical modelling and experimental reconstitution.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Three basic mechanisms of tissue self-organization.
Figure 2: Examples of tissue self-organization in three-dimensional cell culture.
Figure 3: Bistable signal interactions in regional patterning of the optic cup.
Figure 4: Crucial controlling steps in self-driven optic-cup morphogenesis.
Figure 5: Cytosystems dynamics for multicellular emergence biology.

References

  1. Nieuwkoop, P. D. Inductive interactions in early amphibian development and their general nature. J. Embryol. Exp. Morphol. 89, S333–S347 (1985).

    Google Scholar 

  2. Camazine, S., Deneubourg, J. -L., Franks, N. R., Sneyd, J., Theraulaz, G. & Bonabeau, E. Self-Organization in Biological Systems (Princeton Univ. Press, 2001).

    MATH  Google Scholar 

  3. Yates, E. F., Garfinkle, A, Walter, D. O. & Yate, G. B. Self-Organizing Systems: the Emergence of Order (Plenum, 1987).

    Book  Google Scholar 

  4. Chuong, C. M. & Richardson, M. K. Pattern formation today. Int. J. Dev. Biol. 53, 653–658 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  5. Saetzler, K., Sonnenschein, C. & Soto, A. M. Systems biology beyond networks: generating order from disorder through self-organization. Semin. Cancer Biol. 21, 165–174 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. Dobrescu, R. & Purcarea, V. I. Emergence, self-organization and morphogenesis in biological structures. J. Med. Life 4, 82–90 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Whitesides, G. M. & Boncheva, M. Beyond molecules: self-assembly of mesoscopic and macroscopic components. Proc. Natl Acad. Sci. USA. 99, 4769–4774 (2002).

    ADS  CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. Winfree, A. T. Spiral waves of chemical activity. Science 175, 634–636 (1972).

    ADS  CAS  PubMed  Article  Google Scholar 

  9. Velarde, M. G. & Normand, C. Convection. Sci. Am. 243, 92–108 (1980).

    Article  Google Scholar 

  10. Forrest, S. B. & Haff, P. K. Mechanics of wind ripple stratigraphy. Science 255, 1240–1243 (1992).

    ADS  CAS  PubMed  Article  Google Scholar 

  11. Kauffman, S. A. The Origins of Order: Self-Organization and Selection in Evolution. (Oxford Univ. Press, 1993).

    Google Scholar 

  12. Grassé, P. P. La reconstruction du nid et les coordinations inter-individuelles chez Bellicositermes natalensis et Cubitermes sp. La theorie de la stigmergie: Essai d'interpretation des termites. constructeurs. Insectes Sociaux 6, 41–83 (1959).

    Article  Google Scholar 

  13. Bonabeau, E. Stigmergy. Artif. Life 5, 95–96 (1999).

    Article  Google Scholar 

  14. Whitesides, G. M. & Grzybowski, B. Self-assembly at all scales. Science 295, 2418–2421 (2002).

    ADS  CAS  PubMed  Article  Google Scholar 

  15. Caspar, D. L. & Klug, A. Physical principles in the construction of regular viruses. Cold Spring Harb. Symp. Quant. Biol. 27, 1–24 (1962).

    CAS  PubMed  Article  Google Scholar 

  16. Gardner, M. K., Hunt, A. J., Goodson, H. V. & Odde, D. J. Microtubule assembly dynamics: new insights at the nanoscale. Curr. Opin. Cell Biol. 20, 64–70 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Wilson, H. V. On some phenomena of coalescence and regeneration in sponges. J. Exp. Zool. 5, 245–258 (1907).

    Article  Google Scholar 

  18. Townes, P. L. & Holtfreter, J. Directed movements and selective adhesion of embryonic amphibian cells. J. Exp. Zool. 128, 53–120 (1955).

    Article  Google Scholar 

  19. Dan-Sohkawa, M., Yamanaka, H. & Watanabe, K. Reconstruction of bipinnaria larvae from dissociated embryonic cells of the starfish, Asterina pectinifera. J. Embryol. Exp. Morphol. 94, 47–60 (1986).

    CAS  PubMed  Google Scholar 

  20. Takeichi, M. Self-organization of animal tissues: cadherin-mediated processes. Dev. Cell 21, 24–26 (2011).

    CAS  PubMed  Article  Google Scholar 

  21. Togashi, H. et al. Nectins establish a checkerboard-like cellular pattern in the auditory epithelium. Science 333, 1144–1147 (2011). In this article, the authors demonstrate how differential sets of heterophilic adhesion molecules can form chequerboard-like patterns in the epithelial sheet.

    ADS  CAS  PubMed  Article  Google Scholar 

  22. Mori, H., Gjorevski, N., Inman, J. L., Bissell, M. J., Nelson, C. M. Self-organization of engineered epithelial tubules by differential cellular motility. Proc. Natl Acad. Sci. USA. 106, 14890–14895 (2009).

    ADS  CAS  PubMed  Article  PubMed Central  Google Scholar 

  23. Tanner, K., Mori, H., Mroue, R., Bruni-Cardoso, A. & Bissell, M. J. Coherent angular motion in the establishment of multicellular architecture of glandular tissues. Proc. Natl Acad. Sci. USA 109, 1973–1978 (2012).

    ADS  CAS  PubMed  Article  PubMed Central  Google Scholar 

  24. Sawai, S., Thomason, P. A. & Cox, E. C. An autoregulatory circuit for long-range self-organization in Dictyostelium cell populations. Nature 433, 323–326 (2005).

    ADS  CAS  PubMed  Article  Google Scholar 

  25. Thorpe, T. A. History of plant tissue culture. Mol. Biotechnol. 37, 169–180 (2007).

    CAS  PubMed  Article  Google Scholar 

  26. Kondo, S. & Asai, R. A reaction–diffusion wave on the skin of the marine angelfish Pomacanthus. Nature 376, 765–768 (1995). This article is a pioneering paper that suggested Turing-type patterning occurs in stripe formation in the skin of fish.

    ADS  CAS  PubMed  Article  Google Scholar 

  27. Jiang, T. X., Jung, H. S., Widelitz, R. B. & Chuong, C. M. Self-organization of periodic patterns by dissociated feather mesenchymal cells and the regulation of size, number and spacing of primordia. Development 126, 4997–5009 (1999).

    CAS  PubMed  Article  Google Scholar 

  28. Wang, Y., Badea, T. & Nathans, J. Order from disorder: self-organization in mammalian hair patterning. Proc. Natl Acad. Sci. USA 103, 19800–19805 (2006).

    ADS  CAS  PubMed  Article  PubMed Central  Google Scholar 

  29. Sick, S., Reinker, S., Timmer, J. & Schlake, T. WNT and DKK determine hair follicle spacing through a reaction–diffusion mechanism. Science 314, 1447–1450 (2006).

    ADS  CAS  PubMed  Article  Google Scholar 

  30. Plikus, M. V. et al. Self-organizing and stochastic behaviors during the regeneration of hair stem cells. Science 332, 586–589 (2011). In this article the authors report how local interactions between hair follicles contribute to the global pattern of hair regeneration.

    ADS  CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. Green, J. B., Smith, J. C. & Gerhart, J. C. Slow emergence of a multithreshold response to activin requires cell-contact-dependent sharpening but not prepattern. Development 120, 2271–2278 (1994).

    CAS  PubMed  Article  Google Scholar 

  32. ten Berge, D. et al. Wnt signaling mediates self-organization and axis formation in embryoid bodies. Cell Stem Cell 3, 508–518 (2008).

    CAS  Google Scholar 

  33. Marikawa, Y., Tamashiro, D. A., Fujita, T. C. & Alarcon, V. B. Aggregated P19 mouse embryonal carcinoma cells as a simple in vitro model to study the molecular regulations of mesoderm formation and axial elongation morphogenesis. Genesis 47, 103–106 (2009).

    Article  CAS  Google Scholar 

  34. Montesano, R., Matsumoto, K., Nakamura, T. & Orci, L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell 67, 901–908 (1991).

    CAS  PubMed  Article  Google Scholar 

  35. Wei, C., Larsen, M., Hoffman, M. P. & Yamada, K. M. Self-organization and branching morphogenesis of primary salivary epithelial cells. Tissue Eng. 13, 721–735 (2007).

    CAS  PubMed  Article  Google Scholar 

  36. Nelson, C. M., Vanduijn, M. M., Inman, J. L., Fletcher, D. A. & Bissell, M. J. Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science 314, 298–300 (2006).

    ADS  CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Lecaudey, V., Cakan-Akdogan, G., Norton, W. H. & Gilmour, D. Dynamic Fgf signaling couples morphogenesis and migration in the zebrafish lateral line primordium. Development 135, 2695–2705 (2008). This paper describes the mechanism by which FGF signals drive morphogenesis in lateral-line organs during their collective migration.

    CAS  PubMed  Article  Google Scholar 

  38. Friedl, P. & Gilmour, D. Collective cell migration in morphogenesis, regeneration and cancer. Nature Rev. Mol. Cell Biol. 10, 445–457 (2009).

    CAS  Article  Google Scholar 

  39. 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).

    CAS  PubMed  Article  Google Scholar 

  40. Eiraku, E. et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472, 51–56 (2011). This paper describes the how the optic cup self-organization mechanism is driven by local rules in ES cell culture.

    ADS  CAS  PubMed  Article  Google Scholar 

  41. Nakano, T. et al. Self-formation of optic cups and storable stratified neural retina from human ES cells. Cell Stem Cell 10, 771–785 (2012).

    CAS  PubMed  Article  Google Scholar 

  42. Eiraku, M. et al. Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3, 519–532 (2008). This paper describes spontaneous layer formation in ES-cell-derived cortical tissues.

    CAS  PubMed  Article  Google Scholar 

  43. Mariani, J. et al. Modeling human cortical development in vitro using induced pluripotent stem cells. Proc. Natl Acad. Sci. USA 109, 12770–12775 (2012).

    ADS  CAS  PubMed  Article  PubMed Central  Google Scholar 

  44. Suga, H. et al. Self-formation of functional adenohypophysis in three-dimensional culture. Nature 480, 57–62 (2011).

    ADS  CAS  Article  PubMed  Google Scholar 

  45. Sato, T. et al. Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009).

    ADS  CAS  PubMed  Article  Google Scholar 

  46. Sato. T. et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469, 415–418 (2011).

    ADS  CAS  PubMed  Article  Google Scholar 

  47. Spence, J. R., et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105–109 (2011).

    ADS  PubMed  Article  CAS  Google Scholar 

  48. Ikeda, E. et al. Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc. Natl Acad. Sci. USA 106, 13475–13480 (2009).

    ADS  CAS  PubMed  Article  PubMed Central  Google Scholar 

  49. Nakao, K. et al. The development of a bioengineered organ germ method. Nature Methods 4, 227–230 (2007).

    CAS  PubMed  Article  Google Scholar 

  50. Zheng, Y. et al. Organogenesis from dissociated cells: generation of mature cycling hair follicles from skin-derived cells. J. Invest. Dermatol. 124, 867–876 (2005).

    CAS  PubMed  Article  Google Scholar 

  51. Toyoshima, K. E. et al. Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches. Nature Commun. 3, 784 (2012).

    ADS  Article  CAS  Google Scholar 

  52. Halder, G., Callaerts, P. & Gehring, W. J. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267, 1788–1792 (1995).

    ADS  CAS  PubMed  Article  Google Scholar 

  53. Cohn, M. J., Izpisúa-Belmonte, J. C., Abud, H., Heath, J. K. & Tickle, C. Fibroblast growth factors induce additional limb development from the flank of chick embryos. Cell 80, 739–746 (1995).

    CAS  PubMed  Article  Google Scholar 

  54. Adler, R. & Canto-Soler, M. V. Molecular mechanisms of optic vesicle development: complexities, ambiguities and controversies. Dev. Biol. 305, 1–13 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. Fuhrmann, S. Eye morphogenesis and patterning of the optic vesicle. Curr. Top. Dev. Biol. 93, 61–84 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  56. Spemann, H. Über korrelationen in der Entwicklung des Auges. Verh. Anat. Ges. 15, 61–79 (1901).

    Google Scholar 

  57. Hamburger, V. The Heritage of Experimental Embryology (Oxford Univ. Press, 1988).

    Google Scholar 

  58. Li, R. & Bowerman, B. Symmetry Breaking in Biology (Cold Spring Harbor Press 2010).

    Book  Google Scholar 

  59. Turing, A. The chemical basis of morphogenesis. Phil. Trans. R. Soc. Lond. B 237, 37–72 (1952).

    ADS  MathSciNet  MATH  Article  Google Scholar 

  60. Meinhardt, H. & Gierer, A. Pattern formation by local self-activation and lateral inhibition. BioEssays 22, 753–760 (2000).

    CAS  PubMed  Article  Google Scholar 

  61. Kondo, S. & Miura, T. Reaction–diffusion model as a framework for understanding biological pattern formation. Science 329, 1616–1620 (2010).

    ADS  MathSciNet  CAS  PubMed  MATH  Article  Google Scholar 

  62. Economou, A. D. et al. Periodic stripe formation by a Turing mechanism operating at growth zones in the mammalian palate. Nature Genet. 44, 348–351 (2012).

    CAS  PubMed  Article  Google Scholar 

  63. Palmeirim, I., Henrique, D., Ish-Horowicz, D. & Pourquié, O. Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis. Cell 91, 639–648 (1997). This paper demonstrates that vertebrate segmentation occurs in a tissue-autonomous manner that is dependent on its molecular clock.

    CAS  PubMed  Article  Google Scholar 

  64. Palmeirim, I., Dubrulle, J., Henrique, D., Ish-Horowicz, D. & Pourquié, O. Uncoupling segmentation and somitogenesis in the chick presomitic mesoderm. Dev. Genet. 23, 77–85 (1998).

    CAS  PubMed  Article  Google Scholar 

  65. Ferrell, J. E. Jr. Bistability, bifurcations, and Waddington's epigenetic landscape. Curr. Biol. 22, R458–R466 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000).

    ADS  CAS  PubMed  Article  Google Scholar 

  67. Fuhrmann, S. Wnt signaling in eye organogenesis. Organogenesis 4, 60–67 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  68. Yasumoto, K. et al. Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling. EMBO J. 21, 2703–2714 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. Liu, W., Lagutin, O., Swindell, E., Jamrich, M. & Oliver, G. Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate. J. Clin. Invest. 120, 3568–3577 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. Zhao, S. et al. Patterning the optic neuroepithelium by FGF signaling and Ras activation. Development 128, 5051–5060 (2001).

    CAS  PubMed  Article  Google Scholar 

  71. Hoffman, B. D., Grashoff, C. & Schwartz, M. A. Dynamic molecular processes mediate cellular mechanotransduction. Nature 475, 316–323 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  73. Wada, K., Itoga, K., Okano, T., Yonemura, S. & Sasaki, H. Hippo pathway regulation by cell morphology and stress fibers. Development 138, 3907–3914 (2011). References 72 and 73 together demonstrate crucial roles for hippo-related pathways in cellular mechanotransduction, leading to cellular growth and differentiation.

    CAS  PubMed  Article  Google Scholar 

  74. Sansores-Garcia, L. et al. Modulating F-actin organization induces organ growth by affecting the Hippo pathway. EMBO J. 30, 2325–2335 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  75. Taniguchi, K. et al. Chirality in planar cell shape contributes to left-right asymmetric epithelial morphogenesis. Science 333, 339–341 (2011).

    ADS  CAS  PubMed  Article  Google Scholar 

  76. Savin, T. et al. On the growth and form of the gut. Nature 476, 57–62 (2011). This paper is a pioneering report of morphogenetic tissue mechanics, using quantitative measurement of local tissue viscoelasticity.

    ADS  CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    ADS  CAS  PubMed  Article  Google Scholar 

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

    ADS  CAS  PubMed  Article  Google Scholar 

  79. He, L., Wang, X., Tang, H. L. & Montell, D. J. Tissue elongation requires oscillating contractions of a basal actomyosin network. Nature Cell Biol. 12, 1133–1142 (2010).

    CAS  PubMed  Article  Google Scholar 

  80. 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).

    ADS  CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. Eiraku, M., Adachi, T. & Sasai, Y. Relaxation-expansion model for self-driven retinal morphogenesis. BioEssays 34, 17–25 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. Megason, S. G. & Fraser, S. E. Digitizing life at the level of the cell: high-performance laser-scanning microscopy and image analysis for in toto imaging of development. Mech. Dev. 120, 1407–1420 (2003).

    CAS  PubMed  Article  Google Scholar 

  83. Keller, P. J., Schmidt, A. D., Wittbrodt, J. & Stelzer, E. H. Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy. Science 322, 1065–1069 (2008). This article is a pioneering study of in toto imaging for cell-lineage tracing.

    ADS  CAS  PubMed  Article  Google Scholar 

  84. Truong, T. V., Supatto, W., Koos, D. S., Choi, J. M. & Fraser, S. E. Deep and fast live imaging with two-photon scanned light-sheet microscopy. Nature Methods 8, 757–760 (2011).

    CAS  PubMed  Article  Google Scholar 

  85. Tomer, R., Khairy, K., Amat, F. & Keller, P. J. Quantitative high-speed imaging of entire developing embryos with simultaneous multiview light-sheet microscopy. Nature Methods 9, 755–763 (2012).

    CAS  PubMed  Article  Google Scholar 

  86. Krzic, U., Gunther, S., Saunders, T. E., Streichan, S. J. & Hufnagel, L. Multiview light-sheet microscope for rapid in toto imaging. Nature Methods 9, 730–733 (2012).

    CAS  PubMed  Article  Google Scholar 

  87. Helmchen, F. & Denk, W. Deep tissue two-photon microscopy. Nature Methods 2, 932–940 (2005).

    CAS  PubMed  Article  Google Scholar 

  88. Olivier, N. et al. Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy. Science 329, 967–971 (2010).

    ADS  CAS  PubMed  Article  Google Scholar 

  89. Eliceiri, K. W. et al. Biological imaging software tools. Nature Methods 9, 697–710 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  90. Zhong, Q., Busetto, A. G., Fededa, J. P., Buhmann, J. M. & Gerlich, D. W. Unsupervised modelling of cell morphology dynamics for time-lapse microscopy. Nature Methods 9, 711–713 (2012).

    CAS  PubMed  Article  Google Scholar 

  91. Moore, S. W., Keller, R. E. & Koehl, M. A. The dorsal involuting marginal zone stiffens anisotropically during its convergent extension in the gastrula of Xenopus laevis. Development 121, 3131–3140 (1995).

    CAS  PubMed  Article  Google Scholar 

  92. Davidson, L. A. Embryo mechanics: balancing force production with elastic resistance during morphogenesis. Curr. Top. Dev. Biol. 95, 215–241 (2011).

    PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  94. Grashoff, C. et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466, 263–266 (2010).

    ADS  CAS  PubMed  PubMed Central  Article  Google Scholar 

  95. Meng, F. & Sachs, F. Orientation-based FRET sensor for real-time imaging of cellular forces. J. Cell Sci. 125, 743–750 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  96. 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).

    CAS  PubMed  Article  Google Scholar 

  97. Hannezo, E., Prost, J. & Joanny, J. F. Instabilities of monolayered epithelia: shape and structure of villi and crypts. Phys. Rev. Lett. 107, 078104 (2011).

    ADS  CAS  PubMed  Article  Google Scholar 

  98. Karr, J. R. et al. A whole-cell computational model predicts phenotype from genotype. Cell 150, 389–401 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  99. Wu, Y. I. et al. A genetically encoded photoactivatable Rac controls the motility of living cells. Nature 461, 104–108 (2009).

    ADS  CAS  PubMed  PubMed Central  Article  Google Scholar 

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

    ADS  PubMed  PubMed Central  Article  CAS  Google Scholar 

Download references

Acknowledgements

I would like to thank my collaborators, especially M. Eiraku, N. Takata, K. Muguruma and T. Adachi, for stimulating strategic discussion on multicellular self-organization.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshiki Sasai.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Additional information

Reprints and permission information is available at www.nature.com/reprints.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sasai, Y. Cytosystems dynamics in self-organization of tissue architecture. Nature 493, 318–326 (2013). https://doi.org/10.1038/nature11859

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature11859

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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