View Program - 63rd Annual Drosophila Research Conference

During development, interpretation of positional cues by individual cells generates stereotyped patterns of gene expression and cell fate. We study the Drosophila follicular epithelium, where cells integrate input from multiple extracellular signals to choose between discrete anterior and posterior cell fates.
Central to the patterning of this epithelium is the localized activation of the epidermal growth factor receptor (EGFR) by a ligand, Gurken (Grk), secreted by the underlying oocyte. Early in oogenesis, Grk is localized at the posterior and induces expression of the transcription factor Midline (Mid). Later, Grk moves to the dorsal anterior, where it instead induces the transcription factor Mirror (Mirr). The choice between these alternative outcomes depends on the presence of additional localized secreted ligands. Posterior cells experience Grk in the presence of the JAK/STAT pathway ligand Unpaired (Upd), which cooperates with Grk to induce mid while also independently repressing mirr, At the anterior, the BMP signaling ligand Decapentaplegic (Dpp) cooperates with Grk to induce mirr, while independently repressing mid. In addition, there is mutual repression between mid and mirr. We propose that this joint activation and derepression generates a bistable choice between these two EGFR targets, but how a cell interprets and integrates these signals remains unknown.
We address this question by characterizing reporters bearing putative cis-regulatory regions (CRRs) from the mid and mirr loci. We discovered that, for each gene, the response elements for the known regulatory inputs are distributed across two reporters bearing non-overlapping CRRs. Dpp response elements are located in a different mid CRR than those for Upd or Mirr, and Upd response elements are located in a different mirr CRR than those for Dpp or Mid. Reporters with these CRRs differ in expression boundary and dynamics, providing a tool for assessing the contribution of different regulatory inputs to mid and mirr expression . Further analysis of these CRRs suggests that repression of mirr and mid by JAK/STAT signaling and BMP signaling, respectively, requires binding of the signal mediators to cis-elements. We will be investigating the interplay between the different regulatory inputs to mid and mirr and their role in patterning by manipulating these cis-elements in different sequence contexts.

Integration of BMP, JAK/STAT and EGFR signaling during anterior-posterior patterning of the follicular epithlium.