Dietary nutrient-induced quiescence delays neural stem cell proliferation in the Drosophila central brain

Abstract

In the fruit fly Drosophila, neural stem cells (termed neuroblasts) within the brain divide throughout development to produce the larval and adult central nervous system (CNS). Neuroblasts alternate between periods of proliferation and quiescence, and this balance is critical for proper tissue growth and diversity of cell types. Neuroblasts enter a period of quiescence at the end of embryogenesis upon depleting their store of maternal nutrition but reactivate proliferation soon after larval hatching when they consume amino acids during feeding. Neuroblasts in larvae maintained on a diet lacking amino acids likewise halt proliferation and production of daughter cells for extended periods of time. This quiescent state is reversible after reintroduction of dietary amino acids and is presumably an adaptation allowing mobile larvae to secure another nutrient source if faced with starvation. The extent to which such nutrient-induced developmental delays affect the structure and function of the adult brain has not been investigated. Therefore, we used a previously established dietary nutrient deprivation model to halt neuroblast proliferation in larvae for an extended period. These larvae were then reintroduced to nutrients, allowing neuroblasts to reactivate proliferation. Using confocal microscopy, we measured the effect of this treatment on the numbers of mitotic neuroblasts in the central brain and how many daughter cells they produced. Both measures were reduced in delayed larvae compared to controls, despite having access to dietary nutrients for the same amount of time. Follow-up experiments showed that these effects were temporary and neuroblasts returned to their normal proliferative behavior with more recovery time on nutrients. These results elucidate an uninvestigated aspect of plasticity in the developing CNS and lay a foundation for further study of developmental delays on the adult brain.