View Program - 63rd Annual Drosophila Research Conference

During early life neurogenesis, neural stem cells give rise to thousands of morphologically and functionally diverse neurons that will build the adult brain. Ultimately, these neurons form functional circuits, and it is these circuits that allow proper functioning and survival of the adult animal. While neurogenesis is known to be influenced by both intrinsic and extrinsic signalling, we still have a limited understanding of how these signals interact. My work seeks to elucidate the integration of intrinsic and extrinsic signalling by studying how an extrinsic factor, nutrient signalling, and an intrinsic factor, natural genetic variation, interact during nutrient-dependent processes of neurogenesis in Drosophila melanogaster (fly). In order to capture genetic variation reflective of natural populations, I have used a collection of geographically diverse, wild-caught, inbred lines of flies for all experiments. I first characterized neural stem cell, or neuroblast (NB), reactivation, a temporally regulated, nutrient-dependent process of neurogenesis. My work revealed significant differences in the timing of NB reactivation from quiescence when genetically distinct flies are raised in a calorically rich environment. These differences in reactivation could affect the total amount of time that a NB is producing neurons, which could result in changes in the total number of neurons in the adult brain and potentially cause functional differences for the adult fly. Moreover, these results may suggest a genetically encoded basis for variation in neurogenesis.

After observing variation in neurogenesis in a calorically rich environment, I characterized NB reactivation in a calorically poor environment. Preliminary results show that flies with distinct genetic backgrounds respond differently to caloric restriction. Such results may suggest a gene-by-environment interaction during the transition from quiescence to reactivation in flies.

Next, I will continue to build a full timeline from reactivation to termination in larval NBs in calorie rich and calorie poor environments, measure temporally regulated transitions between transcription factors that play a role in neuronal specification, analyze the genomes of the experimental fly lines for genes involved in nutrient dependent steps of neurogenesis, and quantify the neuronal make-up of the adult fly brains. Through this work, I will build a more integrative understanding of how intrinsic and extrinsic cues interact during neurogenesis.

Building an integrative model of how nutrition and natural genetic variation interact during neurogenesis in natural populations of Drosophila melanogaster