IBN-9507406 Tadaatsu Goto Thomas Jefferson University Pattern formation is the process by which embryonic cells form ordered spatial arrangements of cells. This process and the differentiation of embryonic cells make ordered development of embryos possible. An effective system to study pattern formation in development is segmentation in Drosophila, controlled by a hierarchically organized set of genes encoding transcription factors. Molecular events underlying the formation of segments can be considered as a progressive refinement of positional information, reflected in the expression patterns of these genes. Maternal mRNAs for segmentation genes first activate downstream genes in a series of broad, overlapping domains along the anterior- posterior axis; these in turn activate the "pair-rule genes" expressed in 7 regularly spaced stripes, which then activate subordinate genes in 14 stripes. This leads to the formation of 14 repetitive metameres, or segments. One pair-rule gene critical to this cascade is even-skipped (eve). The initial broad stripes of eve expression, that span 4-6 nuclei, become narrow and sharply defined, 1-2 cells in width, as time progresses. This refinement of the pattern apparently enables eve to play a series of roles in regulating other genes with increasing precision. These investigators will explore the mechanisms and function of this refinement. They have already identified a cis-regulatory region call the "late element" in the eve locus that controls the expression of refined stripes; this element seems to be activated by products of other pair-rule genes. The investigators will identify pair-rule gene products that interact with the late element directly. First, they will locate and analyze cis- regulatory sites within the late element critical for interactions, employing a novel transgenic strategy they have developed. Second, they will perform detailed biochemical studies of protein-DNA interactions at these sites. These studies will allow the investigators better understand how eve and other pair-rule genes combine their regulatory effects, contributing to understanding the molecular mechanisms of embryonic development. ***
