Growth control in the Drosophila eye disc by the cytokine Unpaired

A fundamental question in developmental biology is how organ size is controlled. We have previously shown that the area growth rate in the Drosophila eye primordium declines inversely proportionally to the increase in its area. How the observed reduction in the growth rate is achieved is unknown. Here, we explore the dilution of the cytokine Unpaired (Upd) as a possible candidate mechanism. In the developing eye, upd expression is transient, ceasing at the time when the morphogenetic furrow first emerges. We confirm experimentally that the diffusion and stability of the JAK/STAT ligand Upd are sufficient to control eye disc growth via a dilution mechanism. We further show that sequestration of Upd by ectopic expression of an inactive form of the receptor Domeless (Dome) results in a substantially lower growth rate, but the area growth rate still declines inversely proportionally to the area increase. This growth rate-to-area relationship is no longer observed when Upd dilution is prevented by the continuous, ectopic expression of Upd. We conclude that a mechanism based on the dilution of the growth modulator Upd can explain how growth termination is controlled in the eye disc.