Organ Size Coordination by Chemical Signaling

A profound open question in biology is how animals ensure that their body parts have the correct relative proportions given that development is often noisy. For instance, wings of the same fruit fly do not differ in size by more than about 1% in normal conditions. More interestingly, knocking out a single gene (dilp8) responsible for a hormone secreted by the organs in fly larvae leads to increased size asymmetry of 2-3% between left and right wings. Inspired by this example, we model noisy growth of bilaterally symmetric organs and investigate different mechanisms of organ size coordination using a single coordination signal secreted by the organs. We find that generally feedback can help coordinate organs during growth, thus suppressing variability and speeding development, but that no mechanism with a single signal can robustly coordinate final organ sizes. Finally, we show that a particularly appealing mechanism is proportional feedback on growth rate, which best matches the available data on the biological signatures of dilp8 in flies. Our work suggests that while inter-organ feedback is beneficial to development, organs must additionally employ autonomous size specification mechanisms to ensure low asymmetry at the end of growth.