In a system where gene regulation is an isolated developmental process and the key developmental determinants are observable, it is possible to formulate models of gene regulation which are solidly based on experimental facts. We have formulated a model that describes the regulatory effect of one gene on another, as well as the diffusion of gene products between cell nuclei, and their decay. The model is formulated as a set of nonlinear ordinary differential equations for the concentrations of gene products, and also incorporates mitosis. Unknown coefficients in the model are determined by a least squares fit to gene expression data using the computationally intensive method of simulated annealing. We have validated the model for a system of four gap genes and applied it to show that positional information in the presumptive middle body is cooperatively determined by maternal products of the bicoid and hunchback genes.
Current work is directed at extending the model to include pair-rule genes.
We also seek to include promoter substructure in the model. Quantitative imaging of gene products in the blastoderm is a major component of the research effort. A connectionist model of development. Model for cooperative control of positional information in Drosophila by bicoid and maternal hunchback. Reinitz, J .