Constructing quantitative models from qualitative mutant phenotypes: preferences in selecting sensory organ precursors.

Abstract

To study biology from the systems level, mathematical models that describe the time-evolution of the system offer useful insights. Quantitative information is required for constructing such models, but such information is rarely provided. We propose a scheme-based on random searches over a parameter space, according to criteria set by qualitative experimental observations-for inferring quantitative parameters from qualitative experimental results. We used five mutant constraints to construct genetic network models for sensory organ precursor formation in Drosophila development. Most of the models were capable of generating expression patterns for the gene Enhancer of split that were compatible with experimental observations for wild type and two Notch mutants. We further examined factors differentiating the neural fate among cells in a proneural cluster, and found two opposite driving forces that bias the choice between middle cells and the peripheral cells. Therefore, it is possible to build numerical models from mutant screening and to study mechanisms behind the complicated network.