RT Journal Article SR Electronic T1 Physical constraints on growth dynamics guide C. elegans developmental trajectories and animal shape JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.01.438121 DO 10.1101/2021.04.01.438121 A1 Joy Nyaanga A1 Christina Goss A1 Gaotian Zhang A1 Hannah N. Ahmed A1 Elliot J. Andersen A1 Isabella R. Miller A1 Justine K. Rozenich A1 Iris L. Swarthout A1 Jordan A. Vaughn A1 Erik C. Andersen A1 Niall M. Mangan A1 Sasha Shirman YR 2021 UL http://biorxiv.org/content/early/2021/04/02/2021.04.01.438121.abstract AB 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.Author summary Precise growth control is essential to the development of proper adult body size and shape. Although a larger body size can increase an organism’s competitive advantage, an increased body size also requires added time and nutrients to develop. As such, organisms must have mechanisms to both sense and adjust growth during development. Studies of single cells have revealed that proper body size can be achieved using size or time control mechanisms. In multicellular organisms, additional levels of control are required as growth must be differentially regulated across cells, tissues, and organs. We leveraged the roundworm Caenorhabditis elegans as a scalable model to investigate growth control in metazoans. As animals transitioned from one developmental stage to the next, we observed changes in body shape while body size remained constant, suggesting that animals might sense shape to set developmental timing. Two mechanisms likely control growth rate, physical control of feeding rate and metabolic regulation, and we are able to identify developmental periods where each govern growth. Our results demonstrate how physical constraints in tandem with other regulation can be used to broadly control developmental timing and growth rate across diverse organisms.Competing Interest StatementThe authors have declared no competing interest.