MECHANISM OF EVE STRIPE FORMATION

In this paper we analyze the formation of stripes of expression of the pair-rule gene eve. We identify detailed mechanisms which control the formation of stripes 2-5. Each stripe is formed as a result of genera lized activation by bcd and ubiquitous transcription factors combined with localized repression by gap genes. Each of the eight stripe borde rs of these four stripes is shown to be under the control of a particu lar gap gene expression domain. Protein synthesis from eve and its con trolling gap genes begins at the same time, but localized eve expressi on is substantially delayed relative to localized expression of gap do mains. We show that this delay results from a change in the spatial ba lance between activation and repression due to the intensification and refinement of gap domains during cleavage cycle 14. eve stripe format ion is ordered in time; stripe 2 appears earlier than stripes 3-5. We show that this happens because the formation of stripe 2 is less depen dent on gap domain refinement than is the case for stripes 3-5: Each o f stripes 3-5 is controlled by a pair of overlapping gap domains, wher eas stripe 2 is controlled by a disjoint pair of gap domains. Finally, we observe that eve stripes do not form unless Eve protein has an ext remely small diffusivity, and argue that this low diffusivity is a res ult of the apical localization of pair-rule message. This implies that localization of pair-rule message is required for stripe formation. T he essential tool used to obtain these results is the method of gene c ircuits; which is a new approach to the analysis of gene expression da ta. Its purpose is to provide a way to use this data to infer how conc entrations of products of a given gene change with time and how these changes are influenced by the activating or repressing effects of the products of other genes. The gene circuit method is based on three mai n ideas, explained in the paper. First is the choice of protein concen trations as state variables for the description of gene regulation. Se cond is the summary of chemical reaction kinetics by coarse-grained ra te equations for protein concentrations. Third is the use of least squ ares fits to gene expression data to measure phenomenological paramete rs occurring in the gene circuit.