View Program - 63rd Annual Drosophila Research Conference

The precise control of cell growth and division is critical for proper tissue development, integrity, and function. Growth control involves the integration of intrinsic cellular programs with extrinsic cues, including growth factors, hormones, and the availability of nutrients. At the end of Drosophila embryonic development, proliferating neural stem cells, known as neuroblasts, enter into a period of mitotic dormancy called quiescence. Neuroblast exit from quiescence and cell cycle resumption is tightly coupled to nutrient availability; as larvae hatch and begin feeding, amino acids are sensed, resulting in release of Drosophila insulin-like proteins (Dilps) and subsequent activation of the PI3K growth pathway in neuroblasts. Both Dilp2 produced by insulin producing cells (IPCs) in the brain and Dilp6 from glial cells have been shown to mediate the PI3K activation in neuroblasts that results in exit from quiescence. The fat body, a key nutrient sensing tissue, has likewise been shown to be important for both sensing amino acids and producing systemic factors that result in Dilp secretion and neuroblast reactivation in the larval CNS. Here, using animals in which the fat body has been ablated and cultured brain explants from freshly hatched larvae, we demonstrate that the fat body is not required per se for nutrient-dependent reactivation of neuroblasts from quiescence. This suggests that other cell types and tissues capable of amino acid sensing, local brain production of Dilps, and/or uptake of Dilps from IPCs may be capable of driving nutrient-dependent neuroblast reactivation. We further explore this hypothesis using the trans-Tango and DenMark systems to trace pre- and post-synaptic contacts of Dilp2 and Dilp6 producing neurosecretory neurons as well as neurons in the brain expressing the insulin binding protein ImpL2. Using the GAL4/UAS system to express the proapoptotic gene grim and the potassium channel kir2.1 for synaptic silencing, we test the role of specific sets of neuropeptide and neurotransmitter-producing neurons in reactivation of neuroblasts in response to nutrients. Our results shed light on the programs that govern neural stem cell proliferation decisions in response to dietary nutrient availability.

Neural Circuits Involved in Nutrient-Dependent Neuroblast Reactivation