Imaginal Discs Secrete Insulin-Like Peptide 8 to Mediate Plasticity of Growth and Maturation

Animal size is amazingly constant within co-specific individuals and this constancy is even more striking when we compare the left and right sides of bilaterian organisms. To attain such precision, growing organs must be capable to communicate their size to other organs in the organism and to adjust their developmental timing to compensate for local perturbations caused by both internal and external conditions during ontogeny. How they do so remains a long-standing question in biology. We addressed this problem in the imaginal discs of the fruit fly Drosophila melanogaster, which are known to have a remarkable plasticity to regulate their size and the time of maturation, particularly when they suffer lesions. We attempted to identify the protein signal that mediates the plasticity of growth and maturation time that ensures accurate adult normal-size by comparative oligonucleotide microarray. We screened for genes encoding putatively secreted products that were up-regulated in associated with tumour eyetissues, a condition that we and other observed delay maturation time. We identified a gene we named Drosophila insulin-like peptide 8 (dilp8) as the more robustly enriched gene in the tumours. This previous uncharacterized insulin-like peptide was expressed in peripheral tissue and release to circulation, consistent with the predicted hormonal nature. A loss-of-function mutation in dilp8 rescued the developmental delay caused by the presence of eye tumours and also by genotoxin-induced tissue damage. We also demonstrated that a systemic elevation of dilp8 in the absence of growth variations was sufficient to delay maturation time, slowing growth and thereby preserved adult correct size. Adult flies deficient in this hormone displayed left-right asymmetry, mature in a larger scale of time and are more varied in size. Thus, in this novel insulin/relaxin-like peptide encodes the so long sought after hormone that communicates growth between peripheral tissue to mediate the plasticity of growth and maturation that ensures the correct insect size and the symmetry between the two sides.