Computer Modeling


Science's STKE  18 Jul 2000:
Vol. 2000, Issue 41, pp. tw2
DOI: 10.1126/stke.2000.41.tw2

Von Dassow et al. have developed a computer simulation for segmentation based on the Drosophila segment polarity genes. The model was based on the interactions of the products of five genes (wingless, engrailed, hedgehog, cubitus interruptus, and patched) and the repressor fragment of Cubitus interruptus and the Patched-Hedgehog complex. Nearly 50 free parameters, such as binding constants, protein and mRNA half-lives, and cooperativity coefficients, were predicted by the simulation. In order for the simulation to produce the appropriate biological patterns of expression, two factors that bias engrailed expression and Wingless responsiveness needed to be incorporated. The experimental data for autoactivation of Wingless and repression of engrailed by the repressor fragment of Cubitus interruptus justify the addition of these two factors to the model. The computer-generated pattern of expression was stable to wide variations in any individual parameter, and the pattern could be generated with high frequency, even when initial conditions were varied. As Dearden and Akam point out, modeling may become more important for deciphering complex signaling patterns particularly as genome databases and functional proteomics flood us with data.

von Dassow, G., Meir, E., Munro, E.M., and Odell, G.M. (2000) The segment polarity network is a robust developmental module. Nature 406: 188-192. [Online Journal]

Dearden, P., and Akam, M. (2000) Segmentation in silico. Nature 406: 131-132. [Online Journal]