PROJECT SUMMARY Parent Award: Our brain is composed of an immense diversity of neurons that are molecularly, morphologically, and functionally distinct. Understanding how this immense diversity of neuron types is generated and organized to allow us and other adult animals to carry out such a vast array of complex tasks and behaviors is of great importance. By far, most of the neurons in our adult brains are generated during development, either directly or indirectly from the cell divisions of a defined but, rather heterogeneous population of neural stem cells. Molecular differences exist among neural stem cells based on their location and neural stem cell themselves can change their intrinsic genetic programs over time. Research outlined in this proposal is geared towards better understanding of how neural stem cell extrinsic factors integrate with neural stem cell intrinsic factors to control numbers and types of neurons produced through time and space during development. Here, we use the genetically tractable model organism, Drosophila melanogaster, to uncover the genetic pathways and molecular mechanisms regulating neural stem cell proliferation decisions, from quiescence to proliferation, and then termination once development is complete. Our research goals include gaining a better understanding of how dietary nutrient availability affects neural stem cell proliferation decisions. Through genetic and single cell sequencing techniques, we are working to identify the intrinsic differences among these neural stem cell types that distinguish nutrient-dependence versus nutrient- independence. We are also working on determining how dietary nutrients consumed during development regulate neural stem cell temporal programs and thus types and numbers of neurons produced. Altogether, the research outlined here will advance our understanding of neural stem cell proliferation control during development and how dietary nutrient availability affects types and numbers of neurons produced. These insights should stimulate new discoveries in translational stem cell research in the context of normal development and disease states. Supplement request: In this proposal, we seek to better understand the extrinsic, systemic cues that regulate neural stem cell proliferation decisions during development. This award will support technical training and career development activities for a PhD student as the student pursues their dissertation work and prepares for an upcoming NRSA F31 application.