Physical constraints on growth dynamics guide C. elegans developmental trajectories and animal shape

Abstract

Growth control is essential to establish organism size, so organisms must have mechanisms to both sense and adjust growth. Studies of single cells have revealed that size homeostasis can be achieved using distinct control methods: Sizer, Timer, and Adder. In multicellular organisms, mechanisms that regulate body size must not only control single cell growth but also integrate it across organs and tissues during development to generate adult size and shape. To investigate body size and growth control in metazoans, we can leverage the roundworm Caenorhabditis elegans as a scalable and tractable model. We collected precise growth measurements of thousands of individuals throughout larval development, measured feeding behavior to pinpoint larval transitions, and quantified highly accurate changes in animal size and shape during development. We find differences in the growth of animal length and width during larval transitions. Using a combination of quantitative measurements and mathematical modeling, we present two physical mechanisms by which C. elegans can control growth. First, constraints on cuticle stretch generate mechanical signals through which animals sense body size and initiate larval-stage transitions. Second, mechanical control of food intake drives growth rate within larval stages, but between stages, regulatory mechanisms influence growth. These results suggest how physical constraints control developmental timing and growth rate in C. elegans.