Assessment of Transport Mechanisms Underlying the Bicoid Morphogen Gradient
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.
KeywordsBicoid Diffusion Morphogen gradient FRAP Drosophila melanogaster Monte Carlo simulation Modeling
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).
Conflict of interest
The authors declare no conflicts of interest.
- 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.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
- 16.Sample, C., and S. Y. Shvartsman. Multiscale modeling of diffusion in the early Drosophila embryo. Proc. Nat. Acad. Sci. USA. 2010.Google Scholar