Identification and characterization of transcriptional enhancers integrating Notch and other developmental signals: regulation of the Drosophila nab locus

Cell signaling pathways are frequently used in multiple tissue and stage-specific contexts during multicellular development. The integration of these signaling pathways by transcriptional enhancers controls the tissue specific gene expression necessary for proper development. Enhancers are segments of DNA that interpret developmental signals to produce patterns of gene expression. A set of operational rules defines how different enhancers targeted by the same signals interpret and act on these signals. Using the Drosophila model system, my thesis work focuses on determining the operational rules used by developmental enhancers that integrate the Notch signaling pathway with other pathways. During development, the Notch signaling pathway in used to pattern cell territories involved in cell fate determination, and plays a role in differentiation. I first used a computational approach to identify a set of candidate Notch-target enhancers. From this set I carefully studied one specific enhancer from the nab gene that integrates the Notch and Bone Morphogenetic Protein (BMP) signaling pathways in the developing wing. This nab enhancer is a part of a cluster of enhancers that work together to drive the global nab expression pattern during development. Each of these enhancers drives the expected expression patterns as well as atypical expression patterns, which are silenced by adjacent enhancers. These results suggest that Notch targeted enhancers are involved in both tissue specific gene activation and gene silencing.