Skip to main content
Log in

The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

  • Original Article
  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abreu, J. G., Ketpura, N. I., Reversade, B., & De Robertis, E. M. (2002). Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-β. Nat. Cell Biol., 4(8), 599–604.

    Google Scholar 

  • Alber, M., Tilmann, T. G., Hentschel, H. G. E., Kazmierczak, B., Zhang, Y., Zhu, J., & Newman, S. A. (2008). The morphostatic limit for a model of skeletal pattern formation in the vertebrate limb. Bull. Math. Biol., 70(2), 460–483.

    Article  MathSciNet  MATH  Google Scholar 

  • Alberts, B., Johnson, A., Walter, P., Lewis, J., Raff, M., & Roberts, K. (2002). Molecular biology of the cell (5th ed.). New York: Garland Science.

    Google Scholar 

  • Baker, R. E., Gaffney, E. A., & Maini, P. K. (2008). Partial differential equations for self-organization in cellular and developmental biology. Nonlinearity, 21, R251–R290.

    Article  MathSciNet  MATH  Google Scholar 

  • Bard, J., & Lauder, I. (1974). How well does Turing’s theory of morphogenesis work? J. Theor. Biol., 45, 501–531.

    Article  Google Scholar 

  • Bunow, B., Kernevez, J. P., Joly, G., & Thomas, D. (1980). Pattern formation by reaction-diffusion instabilities: applications to morphogenesis in Drosophila. J. Theor. Biol., 84, 629–649.

    Article  MathSciNet  Google Scholar 

  • Carroll, S. B. (2005). Evolution at two levels: on genes and form. PLoS Biol., 3(7), e245.

    Article  Google Scholar 

  • Chen, Y., & Schier, A. F. (2002). Lefty proteins are long-range inhibitors of squint-mediated nodal signaling. Curr. Biol., 12, 2124–2128.

    Article  Google Scholar 

  • Crampin, E. J., Gaffney, E. A., & Maini, P. K. (1999). Reaction and diffusion on growing domains: scenarios for robust pattern formation. Bull. Math. Biol., 61, 1093–1120.

    Article  Google Scholar 

  • Davidson, D. (1983). The mechanism of feather pattern development in the chick.1. the time of determination of feather position. J. Embryol. Exp. Morphol., 74, 245–259.

    Google Scholar 

  • Ermentrout, B., & Lewis, M. (1997). Pattern formation in systems with one spatially distributed species. Bull. Math. Biol., 59, 533–549.

    Article  MATH  Google Scholar 

  • Gaffney, E. A., & Monk, N. A. M. (2006). Gene expression time delays and Turing pattern formation system. Bull. Math. Biol., 68, 99–130.

    Article  MathSciNet  Google Scholar 

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

    Article  Google Scholar 

  • Gilbert, S. F. (2006). Developmental biology (8th ed.). Sunderland: Sinauer.

    Google Scholar 

  • Gregor, T., Bialek, W., de Ruyter van Steveninck, R., Tank, D., & Wieschaus, E. (2005). Kinetics of morphogen gradient formation. Proc. Natl. Acad. Sci. USA, 102, 18403–18407.

    Article  Google Scholar 

  • Harris, M. P., Williamson, S., Fallon, J. F., Meinhardt, H., & Prum, R. O. (2005). Molecular evidence for an activator–inhibitor mechanism in development of embryonic feather branching. Proc. Natl. Acad. Sci. USA, 102(33), 11734–11739.

    Article  Google Scholar 

  • Hentschel, H., Glimm, T., Glazier, J., & Newman, S. (2004). Dynamical mechanisms for skeletal pattern formation in the vertebrate limb. Proc. R. Soc. Lond. B, Biol. Sci., 271(1549), 1713–1722.

    Article  Google Scholar 

  • Jung, H.-S., Francis-West, P. H., Widelitz, R. B., Jiang, T.-X., Ting-Berreth, S., Tickle, C., Wolpert, L., & Chuong, C.-M. (1998). Local inhibitory action of BMPs and their relationships with activators in feather formation: implications for periodic patterning. Dev. Biol., 196(1), 11–23.

    Article  Google Scholar 

  • Kicheva, A., Pantazis, P., Bollenbach, T., Kalaidzidis, Y., Bittig, T., Jülicher, F., & González-Gaitán, M. (2007). Kinetics of morphogen gradient formation. Science, 315, 521–525.

    Article  Google Scholar 

  • Leuzinger, S., Hirth, F., Gerlich, D., Acampora, D., Simeone, A., Gehring, W., Finkelstein, R., Furukubo-Tokunaga, K., & Reichert, H. (1998). Equivalence of the fly orthodenticle gene and the human OTX genes in embryonic brain development of Drosophila. Development, 125(9), 1703–1710.

    Google Scholar 

  • Levy, V., Lindon, C., Harfe, B. D., & Morgan, B. A. (2005). Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Dev. Cell, 9(6), 855–861.

    Article  Google Scholar 

  • Lin, C.-M., Jiang, T. X., Baker, R. E., Maini, P. K., Widelitz, R. B., & Chuong, C.-M. (2009). Spots and stripes: pleomorphic patterning of stem cells via p-ERK-dependent cell chemotaxis shown by feather morphogenesis and mathematical simulation. Dev. Biol., 334(2), 369–382.

    Article  Google Scholar 

  • Lodish, H., Berk, A., Kaiser, C. A., Krieger, M., Scott, M. P., Bretscher, A., Ploegh, H., & Matsudaira, P. (2007). Molecular cell biology (6th ed.). New York: Freeman.

    Google Scholar 

  • Miura, T., & Shiota, K. (2000a). Extracellular matrix environment influences chondrogenic pattern formation in limb bud micromass culture: experimental verification of theoretical models. Anat. Rec., 258, 100–107.

    Article  Google Scholar 

  • Miura, T., & Shiota, K. (2000b). TGFβ2 acts as an activator molecule in reaction-diffusion model and is involved in cell sorting phenomenon in mouse limb micromass culture. Dev. Dyn., 217, 241–249.

    Article  Google Scholar 

  • Miura, T., Shiota, K., Morriss-Kay, G., & Maini, P. K. (2006). Mixed-mode pattern in Doublefoot mutant mouse limb-Turing reaction-diffusion model on a growing domain during limb development. J. Theor. Biol., 240, 562–573.

    Article  MathSciNet  Google Scholar 

  • Moreo, P., Gaffney, E. A., Garcia-Aznar, J. M., & Doblare, M. (2010). On the modelling of biological patterns with mechanochemical models: insights from analysis and computation. Bull. Math. Biol., 72(2), 400–431.

    Article  MathSciNet  MATH  Google Scholar 

  • Mou, C., Jackson, B., Schneider, P., Overbeek, P. A., & Headon, D. J. (2006). Generation of the primary hair follicle pattern. Proc. Natl. Acad. Sci. USA, 103(24), 9075–9080.

    Article  Google Scholar 

  • Mou, C., Thomason, H. A., Willan, P. M., Clowes, C., Harris, W. E., Drew, C. F., Dixon, J., Dixon, M. J., & Headon, D. J. (2008). Enhanced ectodysplasin-a receptor (EDAR) signaling alters multiple fiber characteristics to produce the east Asian hair form. Human Mutat., 29(12), 1405–1411.

    Article  Google Scholar 

  • Mou, C., Pitel, F., Gourichon, D., Vignoles, F., Tzika, A., Tato, P., Yu, L., Burt, D. W., Bed’hom, B., Tixier-Boichard, M., Painter, K. J., & Headon, D. J. (2011). Cryptic patterning of avian skin confers a developmental facility for loss of neck feathering. PLoS Biol., 9(3), e1001028.

    Article  Google Scholar 

  • Murray, J. D. (2003). Mathematical biology II: spatial models and biochemical applications (Vol. II, 3rd ed.). Berlin: Springer.

    Google Scholar 

  • Plikus, M., Wang, W. P., Liu, J., Wang, X., Jiang, T. X., & Chuong, C. M. (2008). Morpho-regulation of ectodermal organs: integument pathology and phenotypic variations in K14-Noggin engineered mice through modulation of bone morphogenic protein pathway. Am. J. Pathol., 164(3), 1099–1114.

    Google Scholar 

  • Pummila, M., Fliniaux, I., Jaatinen, R., James, M. J., Laurikkala, J., Schneider, P., Thesleff, I., & Mikkola, M. L. (2007). Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of BMP activity and induction of Shh expression. Development, 134(1), 117–125.

    Article  Google Scholar 

  • Qian, H., & Murray, J. D. (2001). A simple method of parameter space determination for diffusion-driven instability with three species. Appl. Math. Lett., 14, 405–411.

    Article  MathSciNet  MATH  Google Scholar 

  • Rauch, E. M., & Millonas, M. M. (2004). The role of trans-membrane signal transduction in Turing-type cellular pattern formation. J. Theor. Biol., 226, 401–407.

    Article  MathSciNet  Google Scholar 

  • Sakuma, R., Ohnishi, Y., Meno, C., Fujii, H., Juan, H., Takeuchi, J., Ogura, T., Li, E., Miyazono, K., & Hamada, H. (2002). Inhibition of nodal signalling by lefty mediated through interaction with common receptors and efficient diffusion. Genes Cells, 7, 401–412.

    Article  Google Scholar 

  • Satnoianu, R. A., Menzinger, M., & Maini, P. K. (2000). Turing instabilities in general systems. J. Math. Biol., 41, 493–512.

    Article  MathSciNet  MATH  Google Scholar 

  • Schmidt-Ullrich, R., & Paus, R. (2005). Molecular principles of hair follicle induction and morphogenesis. BioEssays, 27(3), 247–261.

    Article  Google Scholar 

  • Segel, L. A., & Jackson, J. L. (1972). Dissipative structure—explanation and an ecological example. J. Theor. Biol., 37, 545–559.

    Article  Google Scholar 

  • Seirin-Lee, S., & Gaffney, E. A. (2010). Aberrant behaviours of reaction diffusion self-organisation models on growing domains in the presence of gene expression time delays. Bull. Math. Biol., 72, 2161–2179.

    Article  MathSciNet  MATH  Google Scholar 

  • Seirin-Lee, S., Gaffney, E. A., & Monk, N. A. M. (2010). The influence of gene expression time delays on Gierer-Meinhardt pattern formation systems. Bull. Math. Biol., 72, 2319–2360.

    MathSciNet  Google Scholar 

  • Seirin-Lee, S., Gaffney, E. A., & Baker, R. E. (2011). The dynamics of Turing patterns for morphogen-regulated growing domains with cellular response delays. Bull. Math. Biol. doi:10.1007/s11538-011-9634-8.

    Google Scholar 

  • Sengel, P. (1990). Pattern formation in skin development. Int. J. Dev. Biol., 34(1), 33–50.

    Google Scholar 

  • Sharov, A. A., Sharova, T. Y., Mardaryev, A. N., Tommasi di Vignano, A., Atoyan, R., Weiner, L., Yang, S., Brissette, J. L., Dotto, G. P., & Botchkarev, V. A. (2006). Bone morphogenetic protein signaling regulates the size of hair follicles and modulates the expression of cell cycle-associated genes. Proc. Natl. Acad. Sci. USA, 103(48), 18166–18171.

    Article  Google Scholar 

  • Sick, S., Reinker, S., Timmer, J., & Schlake, T. (2006). WNT and DKK determine hair follicle spacing through a reaction-diffusion mechanism. Science, 314(5804), 1447–1450.

    Article  Google Scholar 

  • Solnica-Krezel, L. (2003). Vertebrate development: taming the nodal waves. Curr. Biol., 13, R7–R9.

    Article  Google Scholar 

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

    Article  Google Scholar 

  • White, K. A. J., & Gilligan, C. A. (1998). Spatial heterogeneity in three species, plant-parasite-hyperparasite, systems. Philos. Trans. R. Soc. B, 353, 543–557.

    Article  Google Scholar 

  • Wolpert, L. (1994). Positional information and pattern formation in development. Dev. Genet., 15(6), 485–490.

    Article  Google Scholar 

  • Wolpert, L. (2002). Principles of development (2nd ed.). London: Oxford University Press.

    Google Scholar 

  • Zhang, Y., Tomann, P., Andl, T., Gallant, N. M., Huelsken, J., Jerchow, B., Birchmeier, W., Paus, R., Piccolo, S., Mikkola, M. L., Morrisey, E. E., Overbeek, P. A., Scheidereit, C., Millar, S. E., & Schmidt-Ullrich, R. (2009). Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction. Dev. Cell, 17(1), 49–61.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Václav Klika.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klika, V., Baker, R.E., Headon, D. et al. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation. Bull Math Biol 74, 935–957 (2012). https://doi.org/10.1007/s11538-011-9699-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11538-011-9699-4

Keywords

Navigation