In vertebrates, the arms, legs, fins and wings are neatly aligned on either side of the torso. While this symmetry may seem both unremarkable and perfectly natural, the orderly structure characteristic of each species is in fact the result of a series of intricate processes occurring during embryo formation. In a paper published recently in the journal Nature, EPFL scientists show how surface tension – an entirely mechanical force – influences the final position and lengthwise symmetry of somites, the embryonic building blocks that cause the limb buds to develop. This very same, well-known force is behind the rounded shape of water at the top of a glass and of dew drops on a leaf. The team’s finding provides new insights into the early stages of life, demonstrating for the first time how surface tension, which occurs in all embryonic tissues, drives a key process in vertebrate development.
Attaining symmetry independently of environmental factors
Somites are tiny, blocklike structures that appear on the left and right sides of the neural tube, the precursor to the central nervous system. They form rhythmically and sequentially along the body axis during the early stages of embryo development. These minuscule bulges are the start of the musculoskeletal system, giving rise to the left-right symmetrical segmented ribs, backbones and their associated muscles, a common feature of all vertebrates. It was long thought that somites owed their remarkably precise final left-right symmetry to the action of a genetic oscillator, the so-called segmentation clock. However, this text book view turned out to be wrong.
“Sometimes, somites will initially form on the two sides that are uneven in length and asymmetrical in shape,” explains Sundar Naganathan, a postdoctoral researcher at EPFL’s Timing, Oscillations, and Pattern laboratory. In their research, the scientists set out to understand how this early-stage variation ultimately results in body symmetry. “We demonstrated that symmetry is an emergent property,” says Naganathan.
The shape changes but the volume remains the same
The scientists used various imaging techniques to study zebrafish embryos. They observed a process whereby this imprecise pattern quickly self-corrects, with the somites becoming even in length and distribution on either side of the neural tube around one hour after formation. “We also found that, even though their length changes, the volume of these tiny structures remains the same,” adds Naganathan. “As the length changes, their height and width adjust to compensate.” These initial observations led the researchers to conclude that these changes might be driven by surface tension, a physicochemical property common to all embryonic tissues and connected to the way a liquid interacts with its environment. In order to maintain cohesion between identical molecules, those at the surface have slightly more energy. This structure of the system moves toward a stable configuration that expends the least amount of energy. This, in turn, causes the surface layer to contract and bulge.
Using automated algorithms to analyze terabits of data
Naganathan and his colleagues carried out a series of in vivo and in vitro experiments to prove the link between surface tension and symmetry in living organisms. In one experiment, for instance, they observed that lab-cultured somites take on the same rounded appearance as dew drops on a leaf. But does surface tension provide sufficient force to restore the length of these structures? Thanks to disruptions triggered by proteins known to have an effect on surface tension, the team demonstrated that the somites were no longer the same length. So for the next stage of their research, they used computer modeling techniques to compare and review different models, developing automated algorithms to sift through and analyze several terabits of imaging data. “Our results indicating the role of tissue mechanics in precision of tissue shapes and sizes could be applied to organoid systems, where achieving precise tissue shapes still remains an unsolved problem” adds Naganathan.
The team’s observations all pointed in the same direction. “We concluded that surface tension can facilitate correction of errors in length and symmetry,” says Naganathan. Although the research focused specifically on zebrafish embryos, the findings could have universal significance. “The fact that surface tension is common to developing tissues in all species suggests that this self-correcting process could occur in other vertebrates as well,” he explains.
The scientists plan to continue their research as they look to tackle other unanswered questions about the origins of body symmetry. For instance, having demonstrated how surface tension influences the shape and symmetry of these elementary building blocks, the team still needs to understand how and why limbs of equal size develop on both sides of the torso. “That’s our next big challenge,” says Naganathan. Their research may provide insight into other interesting questions, such as why relatively distant organs such as the eyes and ears are symmetrical in shape, and how body symmetry in general is coordinated with asymmetrical positioning of other organs such as the heart and stomach.