skip to main content


Title: Physical constraints on growth dynamics guide C. elegans developmental trajectories and animal shape.
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.  more » « less
Award ID(s):
1764421
NSF-PAR ID:
10251904
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
bioRxiv
ISSN:
2692-8205
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Most animals develop from juveniles, which cannot reproduce, to sexually mature adults. The most obvious signs of this transition are changes in body shape and size. However, changes also take place in the brain that enable the animals to adapt their behavior to the demands of adulthood. For example, fully fed adult male roundworms will leave a food source to search for mates, whereas juvenile males will continue feeding. The transition to sexual maturity needs to be carefully timed. Too early, and the animal risks compromising key stages of development. Too late, and the animal may be less competitive in the quest for reproductive success. Cues in the environment, such as the presence of food and mates, interact with timing mechanisms in the brain to trigger sexual maturity. But how these mechanisms work – in particular where and how an animal keeps track of its developmental stage – is not well understood. In the roundworm species Caenorhabditis elegans, waves of gene activity, known collectively as the heterochronic pathway, determine patterns of cell growth as animals mature. Through further studies of these worms, Lawson et al. now show that these waves also control the time at which neural circuits mature. In addition, the waves of activity occur inside the nervous system itself, rather than in a tissue that sends signals to the nervous system. Moreover, they occur independently inside many different neurons. Each neuron thus has its own molecular clock for keeping track of development. Several of the genes critical for developmental timekeeping in worms are also found in mammals, including two genes that help to control when puberty starts in humans. If one of these genes – called MKRN3 – does not work correctly, it can lead to a condition that causes individuals to go through puberty several years earlier than normal. Studying the mechanisms identified in roundworms may help us to better understand this disorder. More generally, future work that builds on the results presented by Lawson et al. will help to reveal how environmental cues and gene activity interact to control when we become adults. 
    more » « less
  2. Growth rate and body size are complex traits that contribute to the fitness of organisms. The identification of loci that underlie differences in these traits provides insights into the genetic contributions to development. Leveraging Caenorhabditis elegans as a tractable metazoan model for quantitative genetics, we can identify genomic regions that underlie differences in growth. We measured post-embryonic growth of the laboratory-adapted wild-type strain (N2) and a wild strain from Hawaii (CB4856), and found differences in body size. Using linkage mapping, we identified three distinct quantitative trait loci (QTL) on chromosomes IV, V, and X that are associated with variation in body size. We further examined these size-associated QTL using chromosome substitution strains and near-isogenic lines, and validated the chromosome X QTL. Additionally, we generated a list of candidate genes for the chromosome X QTL. These genes could potentially contribute to differences in animal growth and should be evaluated in subsequent studies. Our work reveals the genetic architecture underlying animal growth variation and highlights the genetic complexity of body size in C. elegans natural populations. 
    more » « less
  3. ABSTRACT Organisms such as jumping froghopper insects and punching mantis shrimp use spring-based propulsion to achieve fast motion. Studies of elastic mechanisms have primarily focused on fully developed and functional mechanisms in adult organisms. However, the ontogeny and development of these mechanisms can provide important insights into the lower size limits of spring-based propulsion, the ecological or behavioral relevance of ultrafast movement, and the scaling of ultrafast movement. Here, we examined the development of the spring-latch mechanism in the bigclaw snapping shrimp, Alpheus heterochaelis (Alpheidae). Adult snapping shrimp use an enlarged claw to produce high-speed strikes that generate cavitation bubbles. However, until now, it was unclear when the elastic mechanism emerges during development and whether juvenile snapping shrimp can generate cavitation at this size. We reared A. heterochaelis from eggs, through their larval and postlarval stages. Starting 1 month after hatching, the snapping shrimp snapping claw gradually developed a spring-actuated mechanism and began snapping. We used high-speed videography (300,000 frames s−1) to measure juvenile snaps. We discovered that juvenile snapping shrimp generate the highest recorded accelerations (5.8×105±3.3×105 m s−2) for repeated-use, underwater motion and are capable of producing cavitation at the millimeter scale. The angular velocity of snaps did not change as juveniles grew; however, juvenile snapping shrimp with larger claws produced faster linear speeds and generated larger, longer-lasting cavitation bubbles. These findings establish the development of the elastic mechanism and cavitation in snapping shrimp and provide insights into early life-history transitions in spring-actuated mechanisms. 
    more » « less
  4. We developed an innovative paper-based platform for high-throughput culturing, trapping, and monitoring of C. elegans. A 96-well array was readily fabricated by placing a nutrient-replenished paper substrate on a micromachined 96-well plastic frame, providing high-throughput 3D culturing environments and in situ analysis of the worms. The paper allows C. elegans to pass through the porous and aquatic paper matrix until the worms grow and reach the next developmental stages with the increased body size comparable to the paper pores. When the diameter of C. elegans becomes larger than the pore size of the paper substrate, the worms are trapped and immobilized for further high-throughput imaging and analysis. This work will offer a simple yet powerful technique for high-throughput sorting and monitoring of C. elegans at a different larval stage by controlling and choosing different pore sizes of paper. Furthermore, we developed another type of 3D culturing system by using paper-like transparent polycarbonate substrates for higher resolution imaging. The device used the multi-laminate structure of the polycarbonate layers as a scaffold to mimic the worm’s 3D natural habitats. Since the substrate is thin, mechanically strong, and largely porous, the layered structure allowed C. elegans to move and behave freely in 3D and promoted the efficient growth of both C. elegans and their primary food, E. coli. The transparency of the structure facilitated visualization of the worms under a microscope. Development, fertility, and dynamic behavior of C. elegans in the 3D culture platform outperformed those of the standard 2D cultivation technique. 
    more » « less
  5. Living systems are composed of molecules that are synthesized by cells that use energy sources within their surroundings to create fascinating materials that have mechanical properties optimized for their biological function. Their functionality is a ubiquitous aspect of our lives. We use wood to construct furniture, bacterial colonies to modify the texture of dairy products and other foods, intestines as violin strings, bladders in bagpipes, and so on. The mechanical properties of these biological materials differ from those of other simpler synthetic elastomers, glasses, and crystals. Reproducing their mechanical properties synthetically or from first principles is still often unattainable. The challenge is that biomaterials often exist far from equilibrium, either in a kinetically arrested state or in an energy consuming active state that is not yet possible to reproduce de novo. Also, the design principles that form biological materials often result in nonlinear responses of stress to strain, or force to displacement, and theoretical models to explain these nonlinear effects are in relatively early stages of development compared to the predictive models for rubberlike elastomers or metals. In this Review, we summarize some of the most common and striking mechanical features of biological materials and make comparisons among animal, plant, fungal, and bacterial systems. We also summarize some of the mechanisms by which living systems develop forces that shape biological matter and examine newly discovered mechanisms by which cells sense and respond to the forces they generate themselves, which are resisted by their environment, or that are exerted upon them by their environment. Within this framework, we discuss examples of how physical methods are being applied to cell biology and bioengineering.

     
    more » « less