Poster Presentation 2014 International Biophysics Congress

Describing space-temporal patterns produced by a bistable switch in developmental gene regulatory network (#374)

Francisco J.P. Lopes 1 , Fernando M.C. Vieira 2 , Paulo Mascarello Bisch 3
  1. Department of Biophysics - Xerém, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
  2. Institute of Chemistry, University of Brasilia, Brasilia, DF, Brazil
  3. Institut of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Pattern formation during morphogenesis is one of the most intriguing problems in biology. In this process, the molecular genetic information is translated into macroscopic spatial expression patterns. In some organisms, like the fruit fly Drosophila Melanogaster, maternal gradients of gene regulatory proteins provide an additional layer of information to the embryo. This so-called positional information produces space-temporal patterns responsible for the cell differentiation that precedes the tissue-organ scale of body organization.

A critical aspect of these biochemical patterns is the sharp borders of their gradients that are essential to determine the fate of neighboring cells. We used a systems biology approach combining dynamical systems theory with experimental and computational techniques. For protein profile characterization we used immunohistochemistry, confocal microscopy and image processing and segmentation. For theoretical modeling, we developed a diffusion-reaction model describing gene regulation at the molecular level (1).

We found that space-dependent bistability plays a critical role in generating sharp borders in gradient profiles. Our model reproduces experimentally determined expression patterns of the developmental gene hunchback and successfully predicts mutant behaviors. We demonstrate that the bistable behavior is produced by the auto-activation of this gene. In addition to the initial asymmetry generated in the embryo by maternal gradients, dynamical behaviors like bistability are critical components in the flux of information from the microscopically stored genetic information to the macroscopic organization of cells and tissues.

  1. Lopes FJP at al (2008). Spatial Bistability Generates hunchback Expression Sharpness in the Drosophila Embryo. PLoS Comput Biol 4(9).