In animals, control of the rate and duration of growth is coordinated by endocrine systems which produce secreted peptide hormones and steroid hormones. Many of the key growth pathways that are crucial for human development, such as the insulin signaling pathway, were first identified and characterised in Drosophila. In insects, developmental transitions are regulated by pulses of production of the steroid hormone ecdysone in the larval prothoracic gland (PG). Multiple environmental factors and signaling pathways regulate ecdysone production. To find new regulators of growth we used RNAi to knockdown a set of candidate neuropeptide and growth factor receptors in the PG using phantom-Gal4. We found that knocking down Adipokinetic hormone receptor (AkhR) causes larval lethality. Knocking down Pigment-dispersing factor receptor (Pdfr) causes a severe developmental delay and increases adult weight. Neither receptor has previously been shown to have a role in the PG. We tested amorphic alleles of AkhR and PdfR (AkhR1, Gronke et al. 2007; PdfR5304, Hyun et al. 2005) and found that homozygous mutants were developmentally delayed and larger than their heterozygous controls. We are currently investigating how these specific receptors perturb growth and interact with the PTTH/Tor and insulin pathways, which are known to operate in the PG to control ecdysone production. Identifying novel growth factor receptors and signaling pathways that regulate developmental timing and body size in Drosophila is not only interesting in its own right, but may prove vital in deepening our understanding of human growth disorders, obesity and cancer.
Gronke et al. 2007, PLoS Biol. 5(6): e137; Hyun et al. 2005, Neuron 48(2): 267-278.