CAREER: Bioelectric mechanisms of brain development

Brain formation arises from neural stem cells which expand and generate diverse populations of neurons through a process known as neurogenesis. The regulation of neurogenesis is vital as proliferation defects cause developmental disorders and cancer. Electrolyte balance and the maintenance of physiological pH are essential for a functional brain. Mutations in pH regulatory proteins cause neurodevelopmental disorders in humans; yet remarkably little is known about how changes in pH regulate brain formation. This project uses the fruit fly to determine the role of pH regulatory molecules during neurogenesis. Cutting-edge techniques will be utilized to discover how pH influences neural stem cell division during brain development. The research plan is tightly integrated with educational and outreach initiatives. Undergraduates will participate in a new research-intensive course identifying electrolyte regulators affecting brain development. Collaborating with Missoula’s science museum, SpectrUM, an exhibit for K-12 students in neurobiology and genetics research will be developed. The combined research, education and outreach proposed will boost numbers of students in science by providing resources and skills to ensure success in a wide range of biological sciences career paths. The major goal of this work is to identify the mechanisms by which changes in pH instruct and facilitate neurogenesis during brain formation. Using Drosophila melanogaster, a well characterized model for neurogenesis, the role of pH regulators sodium/proton exchangers and proton vesicular ATPase in neural stem cell asymmetric division and cell identity will be determined. This investigation will leverage and develop cutting-edge genetic tools and innovative approaches to characterize cellular and subcellular localization of pH regulatory proteins during neural development. In addition, spatially and temporally controlled pH sensors will be employed to resolve dynamic pH-dependent aspects of development that have remained previously elusive. This investigation will discover the molecular mechanisms underlying regulation of neural cell lineage by pH dynamics. This project is jointly funded by the Neural Systems Cluster in IOS of the Directorate for Biological Sciences and the Established Program to Stimulate Competitive Research (EPSCoR) of the National Science Foundation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.