The Surprising Way in Which Metabolism Controls Embryo Growth

Pregnant women rely on a balanced diet and nutritional supplements to provide their babies with the right nutrients and ensure healthy growth. These nutrients contribute to development and provide building blocks for cells that lead to a healthy brain, bones, organs, and immune system.

How Metabolism and Embryonic Development are Linked

While this type of nutritional preparation is helpful during pregnancy, scientists at EMBL have discovered that metabolism—the way cells convert food into energy—does more than just provide energy and building blocks for cells for healthy embryonic development during embryonic development. Metabolism has a surprising signaling effect. By specifically modulating metabolism, the scientists were able to identify a signaling molecule that controls the pace of development.

“We found that as the speed of metabolism increased, a certain developmental clock slowed down,” said Hidenobu Miyazawa, one of the first authors of the new study and a research associate in the Aulehla group at EMBL. “This observation suggested that the role of metabolism is not just to provide energy and biomass for biological processes.” Miyazawa, together with two other first authors and former members of the Aulehla group, Nicole Prior and Jona Rada, as well as other EMBL researchers, discovered that metabolism also has a signaling function. The scientists studied mouse embryos as they formed repetitive body segments that eventually developed into spinal columns. The signaling function of metabolism became clear when they discovered that even tiny amounts of certain metabolites—insufficient to actually supply the cells with energy—could still keep the embryo’s “biological clock” for segment formation running. This clock is called the segmentation clock.

The scientists found an inverse relationship between metabolic activity and the pace of the segmentation clock. This means that the higher the metabolic activity in the cells, the slower the segmentation clock. Surprisingly, they were able to reverse this “slow clock” phenotype by restoring cellular signaling without modulating the metabolism itself. This led them to conclude that metabolic activity influences cell signaling. To find out which important metabolites control the clock rhythm, the scientists turned to an experimental approach based on synchronization theory. Just as your internal body rhythm follows the external day-night cycles, the embryo’s segmentation clock can also adapt to an external signal if it is given regularly. “In this project, we investigated whether a metabolite can serve as a signal to control the segmentation clock,” Miyazawa explained.

Future Studies

Using this unique approach, the scientists discovered that a specific sugar molecule, FBP, is the most important metabolite for regulating the segmentation clock. FBP influences the rhythm of the segmentation clock via an important signaling pathway known as the Wnt signaling pathway. Furthermore, Miyazawa explained that the molecular oscillations associated with the segmentation clock could alter the spatial patterns of the embryo’s body segments, as the research team observed the changes. While this scientific finding is important for basic research, it could also have implications for what scientists will be able to understand and control in the future.

This signaling function of metabolism could reflect how organisms respond to their environment, for example by adapting their development to available food resources. “The findings actually raise an important question: Could metabolism itself act as a pacemaker, linking internal biological clocks to external rhythms in the environment?” said Alexander Aulehla, lead author of the study and director of the Department of Developmental Biology at EMBL. “Since metabolism is naturally linked to external signals and cycles such as the circadian clock, our work showing that metabolism can ‘set’ the segmentation clock supports this idea, which we will test in future studies.”