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.

Turing's next steps: the mechanochemical basis of morphogenesis

Abstract

Nearly 60 years ago, Alan Turing showed theoretically how two chemical species, termed morphogens, diffusing and reacting with each other can generate spatial patterns. Diffusion plays a crucial part in transporting chemical signals through space to establish the length scale of the pattern. When coupled to chemical reactions, mechanical processes — forces and flows generated by motor proteins — can also define length scales and provide a mechanochemical basis for morphogenesis. forces and flows generated by motor proteins — can also define length scales and provide a mechanochemical basis for morphogenesis.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Patterning of biochemical species by reaction–diffusion mechanisms.
Figure 2: Patterning by motor-mediated transport.
Figure 3: Length scales set up by stresses.

References

  1. 1

    Turing, A. M. The chemical basis of morphogenesis. Proc. R. Soc. Lond. B Biol. Sci. 237, 37–72 (1952).

    Google Scholar 

  2. 2

    Gierer, A. & Meinhardt, H. A theory of biological pattern formation. Kybernetik 12, 30–39 (1972).

    CAS  Article  Google Scholar 

  3. 3

    Wolpert, L. Positional information and the spatial pattern of cellular differentiation. J. Theor. Biol. 25, 1–47 (1969).

    CAS  Article  Google Scholar 

  4. 4

    Frohnhöfer, H. N. C. & Nüsslein-Volhard, C. Organization of the anterior pattern in the Drosophila embryo by the maternal gene bicoid. Nature 324, 120–125 (1986).

    Article  Google Scholar 

  5. 5

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

    CAS  Article  Google Scholar 

  6. 6

    Huxley, A. F. & Niedergerke, R. Structural changes in muscle during contraction. Interference microscopy of living cells. Nature 173, 971–976 (1954).

    CAS  Google Scholar 

  7. 7

    Huxley, H. E. & Hanson, J. Changes in the cross-striations of muscle during contraction and stretch and their structural interpretion. Nature 173, 973–976 (1954).

    CAS  Article  Google Scholar 

  8. 8

    Gibbons, I. R. & Rowe, A. J. Dynein: a protein with adenosine triphosphatase activity from cilia. Science 149, 424–426 (1965).

    CAS  Article  Google Scholar 

  9. 9

    Brady, S. T. A novel brain ATPase with properties expected for the fast axonal transport motor. Nature 317, 73–75 (1985).

    CAS  Article  Google Scholar 

  10. 10

    Vale, R. D., Reese, T. S. & Sheetz, M. P. Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 42, 39–50 (1985).

    CAS  Article  Google Scholar 

  11. 11

    Crick, F. Diffusion in embryogenesis. Nature 225, 420–422 (1970).

    CAS  Article  Google Scholar 

  12. 12

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

    Google Scholar 

  13. 13

    Luby-Phelps, K. Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area. Int. Rev. Cytol. 192, 189–221 (2000).

    CAS  Article  Google Scholar 

  14. 14

    Helenius, J., Brouhard, G., Kalaidzidis, Y., Diez, S. & Howard, J. The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends. Nature 441, 115–119 (2006).

    CAS  Article  Google Scholar 

  15. 15

    Gutzeit, H. O. & Koppa, R. Time-lapse film analysis of cytoplasmic streaming during late oogenesis of Drosophila. J. Embryol. Exp. Morphol. 67, 101–111 (1982).

    Google Scholar 

  16. 16

    Goldstein, R. E., Tuval, I. & van de Meent, J.-W. Microfluidics of cytoplasmic streaming and its implications for intracellular transport. Proc. Natl Acad. Sci. USA 105, 3663–3667 (2008).

    CAS  Article  Google Scholar 

  17. 17

    Short, M. B. et al. Flows driven by flagella of multicellular organisms enhance long-range molecular transport. Proc. Natl Acad. Sci. USA 103, 8315–8319 (2006).

    CAS  Article  Google Scholar 

  18. 18

    Baas, P. W., Deitch, J. S., Black, M. M. & Banker, G. A. Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proc. Natl Acad. Sci. USA 85, 8335–8339 (1988).

    CAS  Article  Google Scholar 

  19. 19

    Snider, J. et al. Intracellular actin-based transport: how far you go depends on how often you switch. Proc. Natl Acad. Sci. USA 101, 13204–13209 (2004).

    CAS  Article  Google Scholar 

  20. 20

    Zimyanin, V. L. et al. In vivo imaging of oskar mRNA transport reveals the mechanism of posterior localization. Cell 134, 843–853 (2008).

    CAS  Article  Google Scholar 

  21. 21

    Wilhelm, C. Out-of-equilibrium microrheology inside living cells. Phys. Rev. Lett. 101, 028101 (2008).

    Article  Google Scholar 

  22. 22

    Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    CAS  Article  Google Scholar 

  23. 23

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

    CAS  Article  Google Scholar 

  24. 24

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

    CAS  Article  Google Scholar 

  25. 25

    Zerzour, R., Kroeger, J. & Geitmann, A. Polar growth in pollen tubes is associated with spatially confined dynamic changes in cell mechanical properties. Dev. Biol. 334, 437–446 (2009).

    CAS  Article  Google Scholar 

  26. 26

    Howard, J. Mechanical signaling in networks of motor and cytoskeletal proteins. Annu. Rev. Biophys. 38, 217–234 (2009).

    CAS  Article  Google Scholar 

  27. 27

    Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nature Rev. Mol. Cell Biol. 7, 265–275 (2006).

    CAS  Article  Google Scholar 

  28. 28

    Brown, G. C. & Kholodenko, B. N. Spatial gradients of cellular phospho-proteins. FEBS Lett. 457, 452–454 (1999).

    CAS  Article  Google Scholar 

  29. 29

    Wartlick, O., Kicheva, A. & González-Gaitán, M. Morphogen gradient formation. Cold Spring Harb. Perspect. Biol. 1, a001255 (2009).

    Article  Google Scholar 

  30. 30

    Kalab, P., Weis, K. & Heald, R. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295, 2452–2456 (2002).

    CAS  Article  Google Scholar 

  31. 31

    Caudron, M., Bunt, G., Bastiaens, P. & Karsenti, E. Spatial coordination of spindle assembly by chromosome-mediated signaling gradients. Science 309, 1373–1376 (2005).

    CAS  Article  Google Scholar 

  32. 32

    Kicheva, A. et al. Kinetics of morphogen gradient formation. Science 315, 521–525 (2007).

    CAS  Article  Google Scholar 

  33. 33

    Belenkaya, T. Y. et al. Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans. Cell 119, 231–244 (2004).

    CAS  Article  Google Scholar 

  34. 34

    Yu, S. R. et al. Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules. Nature 461, 533–536 (2009).

    CAS  Article  Google Scholar 

  35. 35

    Driever, W. & Nüsslein-Volhard, C. A gradient of bicoid protein in Drosophila embryos. Cell 54, 83–93 (1988).

    CAS  Article  Google Scholar 

  36. 36

    Gregor, T., Bialek, W., de Ruyter van Steveninck, R. R., Tank, D. W. & Wieschaus, E. F. Diffusion and scaling during early embryonic pattern formation. Proc. Natl Acad. Sci. USA 102, 18403–18407 (2005).

    CAS  Article  Google Scholar 

  37. 37

    Gregor, T., Wieschaus, E. F., McGregor, A. P., Bialek, W. & Tank, D. W. Stability and nuclear dynamics of the bicoid morphogen gradient. Cell 130, 141–152 (2007).

    CAS  Article  Google Scholar 

  38. 38

    Spirov, A. et al. Formation of the bicoid morphogen gradient: an mRNA gradient dictates the protein gradient. Development 136, 605–614 (2009).

    CAS  Article  Google Scholar 

  39. 39

    Abu-Arish, A., Porcher, A., Czerwonka, A., Dostatni, N. & Fradin, C. High mobility of Bicoid captured by fluorescence correlation spectroscopy: implication for the rapid establishment of its gradient. Biophys. J. 99, L33–L35 (2010).

    CAS  Article  Google Scholar 

  40. 40

    Meinhardt, H. The Algorithmic Beauty of Sea Shells (Springer, Berlin; London, 2009).

    Book  Google Scholar 

  41. 41

    Nakamasu, A., Takahashi, G., Kanbe, A. & Kondo, S. Interactions between zebrafish pigment cells responsible for the generation of Turing patterns. Proc. Natl Acad. Sci. USA 106, 8429–8434 (2009).

    CAS  Article  Google Scholar 

  42. 42

    Naoz, M., Manor, U., Sakaguchi, H., Kachar, B. & Gov, N. S. Protein localization by actin treadmilling and molecular motors regulates stereocilia shape and treadmilling rate. Biophys. J. 95, 5706–5718 (2008).

    CAS  Article  Google Scholar 

  43. 43

    Manor, U. et al. Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8. Curr. Biol. 21, 167–172 (2011).

    CAS  Article  Google Scholar 

  44. 44

    Varga, V. et al. Yeast Kinesin-8 depolymerizes microtubules in a length-dependent manner. Nature Cell Biol. 8, 957–962 (2006).

    CAS  Article  Google Scholar 

  45. 45

    Varga, V., Leduc, C., Bormuth, V., Diez, S. & Howard, J. Kinesin-8 motors act cooperatively to mediate length-dependent microtubule depolymerization. Cell 138, 1174–1183 (2009).

    CAS  Article  Google Scholar 

  46. 46

    Howard, J. & Hyman, A. A. Microtubule polymerases and depolymerases. Curr. Opin. Cell Biol. 19, 31–35 (2007).

    CAS  Article  Google Scholar 

  47. 47

    Mayr, M. et al. The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression. Curr. Biol. 17, 488–498 (2007).

    CAS  Article  Google Scholar 

  48. 48

    Stumpff, J., Vondassow, G., Wagenbach, M., Asbury, C. & Wordeman, L. The Kinesin-8 motor Kif18A suppresses kinetochore movements to control mitotic chromosome alignment. Dev. Cell 14, 252–262 (2008).

    CAS  Article  Google Scholar 

  49. 49

    Wargacki, M. M., Tay, J. C., Muller, E. G., Asbury, C. L. & Davis, T. N. Kip3, the yeast Kinesin-8, is required for clustering of kinetochores at metaphase. Cell Cycle 9, 2581–2588 (2010).

    CAS  Article  Google Scholar 

  50. 50

    Salbreux, G., Prost, J. & Joanny, J.-F. Hydrodynamics of cellular cortical flows and the formation of contractile rings. Phys. Rev. Lett. 103, 058102 (2009).

    CAS  Article  Google Scholar 

  51. 51

    Bois, J., Jülicher, F. & Grill, S. Pattern formation in active fluids. Phys. Rev. Lett. 106, 028103 (2011).

    Article  Google Scholar 

  52. 52

    Munro, E., Nance, J. & Priess, J. R. Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev. Cell 7, 413–424 (2004).

    CAS  Article  Google Scholar 

  53. 53

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

    CAS  Article  Google Scholar 

  54. 54

    Riedel-Kruse, I. H., Hilfinger, A., Howard, J. & Jülicher, F. How molecular motors shape the flagellar beat. HFSP J. 1, 192 (2007).

    Article  Google Scholar 

  55. 55

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

    CAS  Article  Google Scholar 

  56. 56

    Hamant, O. et al. Developmental patterning by mechanical signals in Arabidopsis. Science 322, 1650–1655 (2008).

    CAS  Article  Google Scholar 

  57. 57

    Schneider, M. E., Dosé, A. C., Salles, F. T., Chang, W. et al. A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression. J. Neurosci. 26, 10243–10252 (2006).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank N. Goehring, M. Mayer and F. Jülicher for discussions, and I. Tolic-Norrelykke for comments on the manuscript.

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Jonathon Howard, Stephan W. Grill or Justin S. Bois.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Jonathon Howard's homepage

Stephan W. Grill's homepage

Justin S. Bois's homepage

Glossary

Active diffusion

Random motion caused by randomly directed active forces, such as those generated by motor proteins.

Advection

Directed transport driven by motor proteins or bulk fluid flow.

Diffusion

The randomly directed motion of a molecule or particle that causes both mixing and the flux of particles from regions of high concentration to low concentration. Diffusion can be caused by thermal forces — that is, collisions with molecules in solution — or by randomly directed active forces, such as those generated by motor proteins that randomly change their direction.

Diffusion coefficient

The constant of proportionality between the flux and the concentration gradient for a diffusing particle. Diffusion can be thermal or active.

Friction coefficient

The constant or proportionality between a stress gradient and velocity.

Length constant

The distance over which a quantity such as concentration decreases e-fold.

Morphogens

Substances, such as proteins or small molecules, that are non-uniformly distributed in space and can influence cell growth or differentiation.

Patterning

The establishment of features that are much larger than those of the individual molecular components, and which are stereotyped from one cell to another or one organism to another.

Reaction–diffusion mechanism

A patterning process in which a diffusing morphogen undergoing chemical reactions (such as degradation or synthesis) forms a well-defined spatial distribution.

Stress

Force per unit area.

Viscoelastic material

A material that is both elastic (it can be stretched but returns to its original shape) and viscous (it deforms at a finite speed determined by the viscosity and the applied stress).

Viscosity

The constant of proportionality between rates of stress and strain (the relative deformation of a solid body due to a stress).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Howard, J., Grill, S. & Bois, J. Turing's next steps: the mechanochemical basis of morphogenesis. Nat Rev Mol Cell Biol 12, 392–398 (2011). https://doi.org/10.1038/nrm3120

Download citation

Further reading

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