Inter-Organ Growth Coordination Is Mediated by the Xrp1-Dilp8 Axis in Drosophila

Abstract

How organs scale with other body parts is not mechanistically understood. We have addressed this question using the Drosophila imaginal disc model. When the growth of one disc domain is perturbed, other parts of the disc and other discs slow down their growth, maintaining proper inter-disc and intra-disc proportions. We show here that the relaxin-like Dilp8 is required for this inter-organ coordination. Our work also reveals that the stress-response transcription factor Xrp1 plays a key role upstream of dilp8 in linking organ growth status with the systemic growth response. In addition, we show that the small ribosomal subunit protein RpS12 is required to trigger Xrp1-dependent non-autonomous response. Our work demonstrates that RpS12, Xrp1, and Dilp8 form an independent regulatory module that ensures intra- and inter-organ growth coordination during development. All organs adjust their growth trajectory to a local growth perturbation, ensuring proper body proportion. Boulan et al. use the fly model to unravel this inter-organ coordination: growth-impaired organs activate the Xrp1 stress-response pathway, leading to the production of the Dilp8 hormone and the systemic growth inhibition of undamaged organs.