The chemical reactions that cells use to power themselves provide key signals for one of the earliest and most critical steps of an embryo鈥檚 development.
The findings bolster growing evidence that metabolism doesn鈥檛 just supply cells with energy, but can also influence their decision-making around what cell types to become and how to behave, as well as improving our understanding of how the embryo鈥檚 environment influences someone鈥檚 later health.
Just after a mammalian embryo implants in the uterus, its cells lose the ability to form into any cell type and instead assemble into three layers 鈥� an outer ectoderm, an inner endoderm and a middle mesoderm 鈥� in a step called gastrulation. Each of these layers goes on to form different tissues and organs.
Advertisement
Biologists long focused on how genes control developmental processes such as this, but recently revisited old ideas about how metabolism might direct development, fuelled by discoveries that metabolic enzymes and the molecules they produce can also affect cell activity.
鈥淚n the past four or five years, I think people have come back to appreciating metabolism once again,鈥� says at the European Molecular Biology Laboratory in Barcelona, Spain.
With little being known about the role of metabolism in the cellular processes behind gastrulation, Trivedi and his colleagues used mouse stem cells to create structures called gastruloids, which mimic some of the features of gastrulation-stage mouse embryos.
When the researchers added a chemical that blocks a kind of metabolic pathway called glycolysis, which involves extracting energy from glucose, they found that the proportions of the three layers in the gastruloids changed, with the ectoderm expanding at the expense of the mesoderm and endoderm.
In another part of the experiment, when they exposed different gastruloids to rising concentrations of glucose, the proportion of endodermal and mesodermal cells increased.
The team also found that blocking glycolysis reduced the activity of cell signals that are known to trigger mesoderm and endoderm development, but artificially activating these signals in glycolysis-blocked gastruloids restored the development of these two layers without switching glycolysis back on. This suggests that glycolysis exerts its effects by influencing these signals, not by affecting the cell鈥檚 energy supply.
The results bolster recent findings by other researchers who found that changing the balance between different types of metabolism .
This study adds to growing evidence that metabolism could drive cellular decision-making during development and is an example of it controlling mammalian gastrulation, says at Yale School of Medicine, whose team recently showed that to guide specific developmental processes.
鈥淢etabolism has always been seen as life-sustaining, but what if it is life-instructing?鈥� she says. 鈥淚t seems like there is a real connection with how the embryo develops and how it makes different parts.鈥�
Research like this highlights how an embryo鈥檚 environment in the uterus can have a profound effect on its development, says Sozen. Diabetes during pregnancy, for example, . 鈥淪o it鈥檚 really important to understand what happens in gastrulation; it鈥檚 such a landmark event in development,鈥� says Sozen.
bioRxiv
