The effects of nutrient-induced quiescence on neural stem cell proliferation in the Drosophila central brain

Abstract

In the fruit fly, neural stem cells (neuroblasts) residing within a specialized brain niche divide throughout development to produce the adult CNS. Neuroblasts normally transition between a proliferative or quiescent state during development, and this balance is critical for proper tissue growth and neuron production. NBs enter quiescence at the end of embryogenesis when maternal nutrient stores are depleted and reactivate proliferation soon after freshly hatched larvae consume their first meal. This reactivation is regulated by a nutritional checkpoint that requires dietary amino acids. Neuroblasts in larvae maintained on a diet lacking amino acids halt proliferation and production of neurons for extended periods of time, and this state is reversible after reintroduction of amino acids to their diet. Presumably this developmental plasticity is an adaptation that allows mobile larvae to secure another nutrient source, but the extent to which such a delay affects the structure and function of the adult CNS has not been investigated. We used our previously established nutrient deprivation model to halt neuroblast proliferation in larvae for a prolonged period. Using confocal microscopy, we measured the effect of this treatment on both the number of mitotic neuroblasts and how many daughter cells they produced. Both measures of neuroblast proliferation were reduced in delayed larvae compared to controls, despite having access to dietary nutrients for the same amount of time. These results elucidate an uninvestigated aspect of plasticity in the developing CNS and lay the foundation for further functional study of adult brains.