Temporal Progression of Drosophila Neural Stem Cells Promoting Neuronal Diversity

Abstract

How are complex nervous systems generated? During development, a small pool of neural stem cells generates a diverse array of cell type diversity that forms a functional brain. Remarkably, this neuronal diversity is generated in a predictable order. In this dissertation, I report my work in understanding how neural stem cells of the developing Drosophila melanogaster, known as neuroblasts, are temporally patterned. My work has established a single-cell RNA sequencing atlas of the early larval stages of neurogenesis that identified key regulators of how neuroblasts progress from a quiescent to a proliferative state. My subsequent studies focused on neuroblast lineages that generate the central brain of the adult. I show that the transcription factor Seven-up is required for switching the production of early to late neuron identities and progressing Type 2 neuroblasts to the end of their lineage (i.e. death). Finally, I show the temporal transcription factor Castor is required for specifying neuron identities born in early larval Type 2 neuroblast lineages. My work shows significant advancements in understanding how the fly brain is generated and provides fruitful future directions to pursue.