Influence of tissue architecture on STAT-mediated morphogenesis and cell migration

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Nontechnical paragraph:During animal development, cells take on different roles and arrange themselves properly to form tissues and the whole organism. If these processes fail, the developing organism could have birth defects or may die. Much is known about the molecular signals that instruct cells to adopt certain roles or migrate to required places, but cells exist in complex environments, and it is not clear how the physical arrangement of tissues affects cell signaling to each other. Recent studies from the Principal Investigator's research group suggest that small gaps between cells may significantly affect both the diffusion of signals and cell movements. The goal of this project is to characterize the effect of tissue shape on cell signaling and organ development. The researchers will combine genetics, observation of signals in living tissues, and computer modeling. The signal mechanisms identified through this work should function similarly in the development of animals generally. Thus, this project will advance our knowledge of fundamental biological mechanisms; in particular, the biophysical factors that govern development, including pattern formation, joint movements of cells, and regulation of cell-cell signals. The PI will integrate this research with her continued efforts in improving higher education in biology. She will train undergraduate and graduate students in critical thinking and interdisciplinary research methods, expand participation of underrepresented individuals in science by partnering with existing programs, and engage in community outreach efforts. Technical paragraph:To determine how tissue structure influences morphogenesis, the research team specifically investigates the Drosophila ovary. Studying Drosophila has proven to be a powerful strategy to discover new genes and signaling mechanisms that function in many organisms, including humans. In the ovary, the epithelial-derived border cells become motile upon activation of the Janus Kinase/Signal Transducer and Activator of Transcription (Jak/STAT) pathway. During oogenesis, a diffusible activator is released from two follicle cells and functions to turn on STAT signaling in a dose-dependent fashion in nearby cells. Activated cells migrate collectively toward high levels of secreted chemoattractants. Prior work suggests that these signaling events are regulated by conserved mechanisms. The project takes advantage of Drosophila genetics, mathematical modeling, and the relatively simple architecture of the developing egg, which can be imaged live to observe cell types interacting in vivo. Specifically, the researchers will: 1) investigate how the dynamics of a diffusible secreted signal are regulated, and how gaps within tissue architecture shape its signal transduction gradient and resultant cell specification, and 2) determine how the landscape of cells in the microenvironment through which the border cells migrate affects collective cell migration behaviors and local concentrations of secreted guidance cues. Overall, this project will integrate cutting-edge, interdisciplinary research with outstanding educational opportunities for the next generation of potential scientists.