Feedback control of organ size precision is mediated by BMP2-regulated apoptosis in the Drosophila eye

by Tomas Navarro, Antonella Iannini, Marta Neto, Alejandro Campoy-Lopez, Javier Muñoz-García, Paulo S. Pereira, Saúl Ares, Fernando Casares

Biological processes are intrinsically noisy, and yet, the result of development—like the species-specific size and shape of organs—is usually remarkably precise. This precision suggests the existence of mechanisms of feedback control that ensure that deviations from a target size are minimized. Still, we have very limited understanding of how these mechanisms operate. Here, we investigate the problem of organ size precision using the Drosophila eye. The size of the adult eye depends on the rates at which eye progenitor cells grow and differentiate. We first find that the progenitor net growth rate results from the balance between their proliferation and apoptosis, with this latter contributing to determining both final eye size and its variability. In turn, apoptosis of progenitor cells is hampered by Dpp, a BMP2/4 signaling molecule transiently produced by early differentiating retinal cells. Our genetic and computational experiments show how the status of retinal differentiation is communicated to progenitors through the differentiation-dependent production of Dpp, which, by adjusting the rate of apoptosis, exerts a feedback control over the net growth of progenitors to reduce final eye size variability.