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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., (© 2017. Published by The Company of Biologists Ltd.)

The size and shape of organs is species specific, and even in species in which organ size is strongly influenced by environmental cues, such as nutrition or temperature, it follows defined rules. Therefore, mechanisms must exist to ensure a tight control of organ size within a given species, while being flexible enough to allow for the evolution of different organ sizes in different species. We combined computational modeling and quantitative measurements to analyze growth control in the Drosophila eye disc. We find that the area growth rate declines inversely proportional to the increasing total eye disc area. We identify two growth laws that are consistent with the growth data and that would explain the extraordinary robustness and evolutionary plasticity of the growth process and thus of the final adult eye size. These two growth laws correspond to very different control mechanisms and we discuss how each of these laws constrains the set of candidate biological mechanisms for growth control in the Drosophila eye disc., (© 2016. Published by The Company of Biologists Ltd.)