Neuropeptide F receptor acts in the Drosophila prothoracic gland to regulate body size and developmental timing

Kannangara JR1, Henstridge MA1, Parsons LM1, Kondo S2, Mirth CK1 and Warr CG1

  1. School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia.
  2. Invertebrate Genetic Laboratory, National Institute of Genetics, Mishima, Japan.

Drosophila melanogaster is an excellent model organism in which to study the regulation of growth, as many of the major growth factors and signalling pathways are conserved between flies and humans. In Drosophila, growth is primarily regulated by the steroid hormone, ecdysone, which is produced in and secreted from the prothoracic gland in response to various environmental and genetic cues. Regulation of ecdysone biosynthesis in the gland involves a number of neuropeptides, for example the Drosophila insulin-like peptides, which regulate ecdysone production in response to nutrition. Here we identify the receptor for Neuropeptide F (Npf), the fly homologue of mammalian NPY, as a novel regulator of Drosophila growth. Knockdown of Npfrspecifically in the prothoracic gland generates a developmental delay and increased body size. Interestingly, while Npfr mutants also have a developmental delay, they instead have a smaller body size. Likewise, knocking down Npf in Npf-expressing neurons also results in a significant delay to development and smaller body size. These defects can be rescued by feeding larvae ecdysone-enriched food. Furthermore, there is reduced expression of ecdysone biosynthesis genes and reduced ecdysone levels in these animals. This suggests that Npf is involved in regulating ecdysone biosynthesis in the Drosophila prothoracic gland. NPY has been shown to interact with the insulin signalling pathway to regulate energy balance and body size in mammals, thus NPY and Npf may share conserved functions. Studies on Drosophila Npf may therefore further our understanding of human metabolic diseases.