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Assessment of Transport Mechanisms Underlying the Bicoid Morphogen Gradient

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Abstract

Morphogen gradients dictate the spatial patterning of multicellular organisms and are established via transport mechanisms. One of the best-characterized morphogens, Bicoid, acts as a polarity determinant in the Drosophila embryo through spatial–temporal control of gap gene expression. The prevailing model for establishment of the gradient has been localized anterior translation, subsequent diffusion, and spatially uniform degradation, consistent with the observed exponential anterior-posterior decay. However, a recent direct measurement of the Bicoid diffusion coefficient via fluorescence recovery after photobleaching (FRAP) resulted in a surprisingly low estimate, which challenged the prevailing model and led to more complicated active transport models. Here, we reassessed this conclusion using a detailed computational model of the FRAP experiment and analysis. In our model, we found disagreement between the input diffusion coefficient and the resulting estimated diffusion coefficient, as measured by previous methods. By using the model to reproduce the original data, we estimate that Bicoid’s mitotic diffusion coefficient is 3-fold larger than the originally reported value. Thus, the long-standing diffusive transport model still holds.

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References

  1. Bergmann, S., Z. Tamari, E. Schejter, B. Z. Shilo, and N. Barkai. Re-examining the stability of the Bicoid morphogen gradient. Cell 132:15–17, 2008; (author reply 17–18).

    Article  Google Scholar 

  2. Bialek, W., T. Gregor, D. W. Tank, and E. F. Wieschaus. Can we fit all of the data? Response. Cell 132:17–18, 2008.

    Article  Google Scholar 

  3. Brown, E. B., E. S. Wu, W. Zipfel, and W. W. Webb. Measurement of molecular diffusion in solution by multiphoton fluorescence photobleaching recovery. Biophys. J. 77:2837–2849, 1999.

    Article  Google Scholar 

  4. Crick, F. Diffusion in embryogenesis. Nature 225:420–422, 1970.

    Article  Google Scholar 

  5. Driever, W., and C. Nusslein-Volhard. The Bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner. Cell 54:95–104, 1988.

    Article  Google Scholar 

  6. Driever, W., and C. Nusslein-Volhard. A gradient of Bicoid protein in Drosophila embryos. Cell 54:83–93, 1988.

    Article  Google Scholar 

  7. Ephrussi, A., and D. St Johnston. Seeing is believing: the Bicoid morphogen gradient matures. Cell 116:143–152, 2004.

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  10. Hecht, I., W. J. Rappel, and H. Levine. Determining the scale of the Bicoid morphogen gradient. Proc. Nat. Acad. Sci. USA 106:1710–1715, 2009.

    Article  Google Scholar 

  11. Houchmandzadeh, B., E. Wieschaus, and S. Leibler. Establishment of developmental precision and proportions in the early Drosophila embryo. Nature 415:798–802, 2002.

    Google Scholar 

  12. Maxwell, J. C. A Treatise on Electricity and Magnetism. Clarendon Press, 1873.

  13. Porcher, A., and N. Dostatni. The Bicoid morphogen system. Curr. Biol. 20:R249–254, 2010.

    Article  Google Scholar 

  14. Riley, M. R., F. J. Muzzio, H. M. Buettner, and S. C. Reyes. Monte Carlo calculation of effective diffusivities in two- and three-dimensional heterogeneous materials of variable structure. Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Topics 49:3500–3503, 1994.

    Google Scholar 

  15. Rubart, M. Two-photon microscopy of cells and tissue. Circ. Res. 95:1154–1166, 2004.

    Article  Google Scholar 

  16. Sample, C., and S. Y. Shvartsman. Multiscale modeling of diffusion in the early Drosophila embryo. Proc. Nat. Acad. Sci. USA. 2010.

  17. Spirov, A., K. Fahmy, M. Schneider, E. Frei, M. Noll, and S. Baumgartner. Formation of the Bicoid morphogen gradient: an mRNA gradient dictates the protein gradient. Development 136:605–614, 2009.

    Article  Google Scholar 

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

    Article  Google Scholar 

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Acknowledgments

The authors would like to thank Odde lab group members D. Seetapun and M. Gardner for computation technical support. Funding provided by National Institutes of Health (NIGMS 071522 and NIBIB T32EB008389).

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The authors declare no conflicts of interest.

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Correspondence to David J. Odde.

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Associate Editor Edward Guo oversaw the review of this article.

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Castle, B.T., Howard, S.A. & Odde, D.J. Assessment of Transport Mechanisms Underlying the Bicoid Morphogen Gradient. Cel. Mol. Bioeng. 4, 116–121 (2011). https://doi.org/10.1007/s12195-010-0157-4

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  • DOI: https://doi.org/10.1007/s12195-010-0157-4

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