An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control

Background: Size regulation is fundamental in developing multicellular orga nisms and occurs through the control of cell number and cell size. Studies in Drosophila have identified an evolutionarily conserved signaling pathway that regulates organismal size and that includes the Drosophila insulin re ceptor substrate homolog Chico, the lipid kinase P1(3)K (Dp110), DAkt1/dPKB , and dS6K. Results: We demonstrate that varying the activity of the Drosophila insulin receptor homolog (DInr) during development regulates organ size by changin g cell size and cell number in a cell-autonomous manner. An amino acid subs titution at the corresponding position in the kinase domain of the human an d Drosophila insulin receptors causes severe growth retardation. Furthermor e, we show that the Drosophila genome contains seven insulin-like genes tha t are expressed in a highly tissue- and stage-specific pattern. Overexpress ion of one of these insulin-like genes alters growth control in a DInr-depe ndent manner. Conclusions: This study shows that the Drosophila insulin receptor autonomo usly controls cell and organ size, and that overexpression of a gene encodi ng an insulin-like peptide is sufficient to increase body size.