Developmental delay ensures global tissue size robustness upon local induction of apoptosis

The capacity of our tissues to cope with external and internal stress relies on the tight coupling between cell proliferation, cell growth and cell death. This coupling is assumed to be based on compensatory proliferation, where local mitogenic signals and mechanical inputs generated by dying cells promote neighbouring cell proliferation. However, compensatory proliferation was mostly studied in the context of massive death induction, irradiation, surgical tissue ablation or upon genetic perturbation of apoptosis execution. It remains thus unclear whether the same mechanism operates during physiological programmed cell death or upon mild induction of apoptosis, especially in vivo. Here, we use the Drosophila prospective wing (the larval wing disc), to study the impact of local induction of apoptosis on tissue size and proliferation pattern. We first confirmed that the wing could recover its final size and compensate for mild induction of apoptosis. However, using spatial statistics we found surprisingly that local induction of death is not associated with any local increase of proliferation, could it be upon clonal or compartment induction of apoptosis. Compensation is driven instead by a JNK dependant delay of growth and lengthening of the larval stage which is required to reach the final tissue target size. These results suggest that compensation is here driven by a global response rather that a local proliferation induction. Accordingly, while total tissue size is maintained despite local induction of apoptosis, this mechanism fails to correct the local reduction of cell number, hence modulating wing shape and proportion. Overall, this study opens novel perspectives on tissue size regulation and outlines the context-dependency of compensatory mechanisms.