Unraveling Neural Diversity: Decoding the Cellular and Molecular Mechanisms of Neural Circuit Formation and Function in the Drosophila Central Complex

Summary: A key question in neurobiology is how neural stem cells (NSCs) produce the vast diversity of neural subtypes required for precise control of behavior. The human cortex is generated from a specialized population of outer radial glia NSCs (oRGs) in the outer subventricular zone, which divide to produce

intermediate neural progenitors (INPs) that themselves divide to produce 8-12 neurons. Drosophila Type II NSCs (T2 NSCs) divide in a similar pattern and generate INPs to produce most neural cells of the central complex (CX)— a conserved brain region across insect species involved in producing complex high-level

behavior. Thus, T2 NSCs are a good model for investigating the genetic mechanisms of neural diversity adopted by neural progenitors across species. We previously discovered a series of transcription factors (TFs) and RNA-binding proteins (RBPs) that are sequentially expressed in T2 NSCs and INPs over

developmental time. These are ideal candidates for specifying the identity of the CX lineages through combinatorial temporal patterning. Here, using an innate goal-directed behavior in flies— odor-guided food search—associated CX circuit, we will identify which temporally expressed TFs and RBPs play a role in

specifying olfactory navigation circuitry and determine the role of these genes in specifying the number, morphology, and identity of each circuit element (Aim 1). Next, we will use genetic birthdating to determine the lineage and birthtime of each circuit element and to examine the link between birth timing and function

in a single T2 NSC lineage—DL1 (Aim 2). Finally, our proposed training, mentoring, and science outreach activities through the Pueblo Brain Science program in New Mexico will target trainees at multiple levels and will improve science education awareness and promote diversity in neuroscience (Aim 3). While

investigating mechanisms regulating neural diversity, our long-term goal is to make the neuroscience field diverse through training, mentoring, and promoting science education in resource-limited and historically neglected Pueblo communities. As many of the identified factors have human homologs, our results will

identify conserved principles governing the development of CX and provide insights into the development of the human cortex.