Date of Award
Master of Science in Integrative Biology (MSIB)
First Committee Member
Second Committee Member
The specification and differentiation of muscle precursor cells, or myoblasts, by the action of the mesodermal and muscle transcription regulator Twist is a key event in the formation of the Drosophila larval musculature. Akirin, a highly conserved nuclear protein, appears to play a critical role in the regulation of Twist-dependent gene expression during mesodermal specification and muscle development. Specifically, Akirin serves as a cofactor to promote interactions between regulatory transcription factors and multisubunit Brahma SWI/SNF-class chromatin remodeling complex to impact gene expression across varying targets. Using a genetic interaction screen in Drosophila, we have begun to identify other Akirin interacting proteins that participate in the process of muscle specification, patterning, and development. Our screening method has identified a number of proteins that genetically interact with Akirin during muscle patterning in the embryo, including pannier and taf4 which both are involved in general transcription initiation. Importantly, we have identified a novel interaction between Akirin and the NuRD chromatin remodeling complex. These results also show context-dependent roles of Akirin at the transcriptional level, as interactions with SWI/SNF family function to facilitate gene expression, and interactions with NuRD family may function repress transcriptional activities. We have extended these studies to map the regions of the Akirin protein that are necessary for such interactions during embryonic muscle development. However, we tried and failed to demonstrate a physical link between Akirin and Twist using the methods in this thesis. By identifying new intermolecular partners for Akirin during myogenesis, we have shed new light on the molecular action of Akirin during embryonic development.