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The Influence of Gene Expression Time Delays on Gierer–Meinhardt Pattern Formation Systems

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Abstract

There are numerous examples of morphogen gradients controlling long range signalling in developmental and cellular systems. The prospect of two such interacting morphogens instigating long range self-organisation in biological systems via a Turing bifurcation has been explored, postulated, or implicated in the context of numerous developmental processes. However, modelling investigations of cellular systems typically neglect the influence of gene expression on such dynamics, even though transcription and translation are observed to be important in morphogenetic systems. In particular, the influence of gene expression on a large class of Turing bifurcation models, namely those with pure kinetics such as the Gierer–Meinhardt system, is unexplored. Our investigations demonstrate that the behaviour of the Gierer–Meinhardt model profoundly changes on the inclusion of gene expression dynamics and is sensitive to the sub-cellular details of gene expression. Features such as concentration blow up, morphogen oscillations and radical sensitivities to the duration of gene expression are observed and, at best, severely restrict the possible parameter spaces for feasible biological behaviour. These results also indicate that the behaviour of Turing pattern formation systems on the inclusion of gene expression time delays may provide a means of distinguishing between possible forms of interaction kinetics. Finally, this study also emphasises that sub-cellular and gene expression dynamics should not be simply neglected in models of long range biological pattern formation via morphogens.

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References

  • Alberts, B., Johnson, A., Walter, P., Lewis, J., Raff, M., Roberts, K., 2002. Molecular Biology of the Cell, 5th edn. Garland, New York.

    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 

  • Baron, M., Aslam, H., Flasza, M., et al., 2002. Multiple levels of notch signal regulation (review). Mol. Membr. Biol. 19, 27–38.

    Article  Google Scholar 

  • Beguinot, L., Lyall, R.M., Willingham, M.C., Pastan, I., 1984. Down-regulation of the epidermal growth factor receptor in kb cells is due to receptor internalization and subsequent degradation in lysosomes. Proc. Natl. Acad. Sci. 81, 2384–2388.

    Article  Google Scholar 

  • Chen, Y., Schier, A., 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 

  • Eldar, A., Dorfman, R., Weiss, D., Ashe, H., Shilo, B.Z., Barkai, N., 2002. Robustness of the BMP morphogen gradient in drosophila embryonic patterning. Nature 419, 304–308.

    Article  Google Scholar 

  • Entchev, E.V., Schwabedissen, A., Gonzalez-Gaitan, M., 2000. Gradient formation of the TGF-β homolog Dpp. Cell 103, 981–991.

    Article  Google Scholar 

  • Fischer, J.A., Eun, S.H., Doolan, B.T., 2006. Endocytosis, endosome trafficking, and the regulation of drosophila development. Annu. Rev. Cell Dev. Biol. 22, 181–206.

    Article  Google Scholar 

  • Gaffney, E.A., Monk, N.A.M., 2006. Gene expression time delays and Turing pattern formation systems. 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 

  • 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 

  • Iratini, R., Yan, Y.T., Chen, C., 2002. Drap1 gastrulation by the transcriptional corepressor inhibition of excess nodal signaling during mouse. Science 298, 1996–1999.

    Google Scholar 

  • Jing, X.H., Zhou, S.M., Wang, W.Q., Chen, Y., 2006. Mechanisms underlying long- and short-range nodal signaling in zebrafish. Mech. Dev. 123, 388–394.

    Article  Google Scholar 

  • Juan, H., Hamada, H., 2001. Roles of nodal-lefty regulatory loops in embryonic patterning of vertebrates. Genes Cells 6, 923–930.

    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, 11–23.

    Article  Google Scholar 

  • Kimmel, C.B., Ballard, W.W., Kimmel, S.R., Ullmann, B., Schilling, T.F., 1995. Stages of embryonic development of the zebrafish. Dev. Dyn. 203, 253–310.

    Google Scholar 

  • Koch, A.J., Meinhardt, H., 1994. Biological pattern formation: from basic mechanisms to complex structures. Rev. Mod. Phys. 66(4), 1481–1507.

    Article  Google Scholar 

  • Krezel, L.S., 2003. Vertebrate development: Taming the nodal waves. Curr. Biol. 13, R7–R9.

    Article  Google Scholar 

  • Lewis, J., 2003. Autoinhibition with transcriptional delay: A simple mechanism for the zebrafish somitogenesis oscillator. Curr. Biol. 13, 1398–1408.

    Article  Google Scholar 

  • Miura, T., Maini, P.K., 2004. Speed of pattern appearance in reaction-diffusion models: Implications in the pattern formation of limb bud mesenchyme cells. Bull. Math. Biol. 66, 627–649.

    Article  MathSciNet  Google Scholar 

  • Miura, T., Shiota, K., 2000. 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 

  • Morton, K.W., Mayers, D.F., 1994. Numerical Solution of Partial Differential Equations. Cambridge University Press, Cambridge.

    MATH  Google Scholar 

  • Murray, J.D., 1993. Mathematical Biology, 2nd edn. Springer, Berlin.

    MATH  Google Scholar 

  • Page, K.M., Monk, N.A.M., Maini, P.K., 2007. Speed of reaction diffusion in embryogenesis. Phys. Rev. E 76, 011902.

    MathSciNet  Google Scholar 

  • Piddini, E., Vincent, J., 2003. Modulation of developmental signals by endocytosis: different means and many ends. Curr. Cell Biol. 15, 474–481.

    Article  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 

  • Roy, C.L., Wrana, J.L., 2005. Clathrin- and nonclathrin-mediated endocytic regulation of cell signaling. Nat. Rev. Mol. Cell Biol. 6, 112–126.

    Article  Google Scholar 

  • Schier, A.F., 2003. Nodal signaling in verterbrate development. Rev. Cell Dev. Biol. 19, 589–621.

    Article  Google Scholar 

  • Schnakenberg, J., 1979. Simple chemical reaction systems with limit cycle behaviour. J. Theor. Biol. 81, 389–400.

    Article  MathSciNet  Google Scholar 

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

    Article  Google Scholar 

  • Sorkin, A., von Zastrow, M., 2002. Signal transduction and endocytosis: close encounters of many kinds. Nat. Rev. Mol. Cell Biol. 3, 600–614.

    Article  Google Scholar 

  • Stoscheck, C.M., Carpenter, G., 2002. Down-regulation of egf receptors: direct demonstration of receptor degradation in human fibroblasts. J. Cell Biol. 98, 1048–1053.

    Article  Google Scholar 

  • Tennyson, C.N., Klamut, H.J., Worton, R.G., 1995. The human dystrophin gene requires 16 hr to be transcribed and is contranscriptionally spliced. Nat. Gen. 9, 184–190.

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Varea, C., Hernandez, D., Barrio, R.A., 2007. Soliton behaviour in a bistable reaction diffusion model. J. Math. Biol. 54, 797–813.

    Article  MathSciNet  MATH  Google Scholar 

  • Veflingstad, S.R., Plahte, E., Monk, N.A.M., 2005. Effect of time delay on pattern formation: Competition between homogenisation and patterning. Physica D 207, 254–271.

    MathSciNet  MATH  Google Scholar 

  • Wells, A., Welsh, J.B., Lazar, C.S., Wiley, H.S., Gill, G.N., Rosenfeld, M.G., 1990. Ligand-induced transformation by a noninternalizing epidermal growth factor receptor. Science 247, 962–964.

    Article  Google Scholar 

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Seirin Lee, S., Gaffney, E.A. & Monk, N.A.M. The Influence of Gene Expression Time Delays on Gierer–Meinhardt Pattern Formation Systems. Bull. Math. Biol. 72, 2139–2160 (2010). https://doi.org/10.1007/s11538-010-9532-5

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