Math Modeling Key to Uncovering Secrets of Embryo Development

July 18, 2007

Collaboration between biologists specializing in the fruit fly (Drosophila melanogaster) and scientists who design mathematical models has brought to light mechanisms underlying embryo development. The results are said to confirm the hypothesis that the gene network — in both vertebrates and insects — has been maintained across evolution because it is highly stable and robust.

Marco Milán of the Institute for Research in Biomedicine, in Barcelona, and his colleagues studied the signals that guide wing development in Drosophila. These signals are generated from a set of cells grouped into different segments or compartments that never mix with one another. They enable the symmetrical construction of the dorsal and ventral parts of the wings, starting from a given limit or border. This process of subdivision into compartments also takes place during the formation of the vertebrate central nervous system, and the genes and signaling pathways involved are conserved in both Drosophila and vertebrate species.

While biologists had an intuitive sense of how the limit or border between these compartments was generated, there had been no systematic study that took into account all relevant elements. Therefore, Milán and his team made use of advanced mathematical models developed at the Center for Research in Theoretical Chemistry, in Barcelona, by Javier Buceta and his collaborators.

In order to study the stability of the system, the scientists conducted 45,000 in silico experiments, introducing variations in twenty parameters. The results enabled them to identify the most important system parameters. They showed that the biological mechanism maintained its functionality in more than 90% of the analyzed cases.

As Milán explained: "Thanks to this computer simulation we have found a new genetic function that ensures the stability of the system and has enabled us to test its robustness. This study shows that modeling is a highly useful tool for describing in silico new properties of a biological system and being able to corroborate them subsequently in vivo."

Buceta indicated that "the advantage of these modeling techniques is that they can simulate genetic and cell interactions as a set of mathematical equations and, therefore, to determine the feasibility of a biological mechanism."

The researchers report their results in the paper "Robustness and Stability of the Gene Regulatory Network Involved in DV Boundary Formation in the Drosophila Wing," published on July 11 by PloS One.

Source: Institute for Research in Biomedicine, July 11, 2007; PLoS One, July 11, 2007