Formation and Function of Insulin-producing Neurons in Drosophila. (360G-Wellcome-083559_Z_07_Z)

Insulin and IGFs are key coordinators of growth and metabolism in multicellular organisms. I have identified a set of neurons that express Ilp7, one of the Drosophila insulin-like peptides. These neurons are distinct from the known insulin-producing cells of the Drosophila brain that secrete into the circulation and regulate global growth. Instead, Ilp7 neurons contact the hindgut muscles, thus raising the possibility that they regulate local gut functions. This proposal is aimed at: 1) characte rizing the developmental and physiological functions of Ilp7 neurons 2) identifying new factors regulating the survival and differentiation of Ilp7 neurons. To investigate the functions of Ilp7 neurons, I will use RNA interference to downregulate Ilp7 expression and the Gal4-UAS system to silence/ablate these neurons. Gut development and physiology will be assessed using defined local and whole-organismal parameters. To identify new genes specifying Ilp7 identity, I will carry out a high-through put F1 screen of pre-mapped mutant lines. The readout for this screen utilises a double reporter line, allowing Ilp7 neurons to be visualised in living embryos under the microscope. Finally, in a candidate gene approach, I will investigate the mechanisms by which homologues of known vertebrate insulin and enteric regulators control insulin production in Ilp7 neurons.