Insulin receptor-mediated organ overgrowth in Drosophila is not restricted by body size

Abstract.

Recent studies have demonstrated that insulin receptor (Inr) signalling plays an important role in determining organ size and maintaining proportionality in normal animals. However, it is unclear whether the activity of this pathway in a developing organ is invariably a dominant determinant of its mass or whether size can be restricted by other non-autonomous growth regulatory mechanisms if a tissue starts to outgrow the rest of the body. To test this in Drosophila, we induced excess Inr-dependent growth by removal of the Inr signalling antagonist, DPTEN, in the eyes of flies with dramatically different body sizes. Although our data suggest a very limited level of growth competition between organs in animals with giant eyes, there do not appear to be mechanisms by which neighbouring structures substantially inhibit eye overgrowth, even when the resulting organ is many times enlarged relative to the rest of the animal. Overall, our results support a simple model in which organs are normally maintained in proportion to each other, primarily because they all respond similarly to levels of insulin-like factors and other growth regulators. Given the evolutionarily conserved role of insulin receptor signalling in growth control, our data may also help to explain why this pathway is so frequently hyperactivated in mammalian tumours.