Members of the insulin family of peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. Here we show that Drosophila insulin-like peptide 6 (DILP6), which is structurally similar to vertebrate insulin-like growth factor (IGF), is predominantly expressed in the fat body, a functional equivalent of the vertebrate liver and adipocytes. This expression occurs during the postfeeding stage under the direct regulation of ecdysteroid. We further reveal that dilp6 mutants show growth defects during the postfeeding stage, which results in reduced adult body size through a decrease in cell number. This phenotype is rescued by fat body-specific expression of dilp6. These data indicate that DILP6 is a functional, as well as a structural, counterpart of vertebrate IGFs. Our data provide in vivo evidence for a role of ILPs in determining adult body size through the regulation of postfeeding growth.
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We thank P. Léopold for sharing unpublished data, and E. Hafen and T. Neufeld for stocks. M.B.O. is an investigator with the Howard Hughes Medical Institute. This work was supported by Grants-in-Aid for Scientific Research (20,570,056) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN) of Japan.