Ultra-sensitive coupling between organ growth and size by YAP-1 ensures uniform body plan proportions in C. elegans

Abstract

AbstractImbalance between the growth rate of different organs can amplify to large deviations of their size proportions during development. We show that, for the C. elegans pharynx, such size divergence is prevented by reciprocal coordination of pharyngeal growth with other tissues. Live imaging of hundreds of individuals revealed that small pharynxes grow more rapidly than large pharynxes, catching up in volume during development. Moreover, pharynx-to-body size proportions were robust to even strong tissue-specific inhibition of mTORC1 and insulin signalling. Tissue-specific depletion of these pathways slowed-down the growth of the respective tissue and additionally triggered a systemic growth response that ensured appropriate organ size proportions. By mathematical modelling, we show that the conservation of proportions requires a bi-directional ultra-sensitive coupling of body growth and pharynx size that cannot be explained by a reduction of food uptake alone. Instead, organ growth coordination requires regulation by the mechano-transducing transcriptional co-activator YAP/yap-1. Knock-down of yap-1 makes animals sensitive to tissue-specific inhibition mTORC1 inhibition, causing a disproportionate pharynx and developmental arrest. Our data suggests that mechano-transduction tightly coordinates organ growth during C. elegans development to ensure the uniformity of body plan proportions among individuals.