Metabolism as a hidden architect of embryonic neurodevelopment

“I am honored to receive the Lundbeck Experiment Grant,” says Kafkia. “It offers an opportunity to pursue a fundamental, high-risk idea that has a vision for neuroscience that can benefit society.” 

Traditionally, metabolism is viewed as the body’s power system, fueling cells with nutrients and energy required for growth. Kafkia’s project proposes a shift, asking whether metabolism in the early embryo is not merely growth supportive or reflect developmental progression but rather may serve as a signal (morphogen) that instructs and patterns early neuronal development. A well-known example that illustrates this concept is folic acid. Pregnant women take folic acid supplements because deficiencies increase the risk of neural tube defects, an early disruption during brain development. Folic acid is a metabolite directly linking nutrition, metabolism, and neurological development. “This shows us that metabolites aren’t just passive bystanders; they can influence how the nervous system develops by acting as a code translating environmental cues into neural architectures,” she explains 

Yet, scientists still know little about how metabolism shapes brain development in the embryo. To address this gap, Kafkia will use advanced isotope-tracing methods to study mouse embryos at different developmental stages, allowing her to observe metabolic activities in vivo (in living mouse embryos). By feeding pregnant mice nutrients with specially labeled forms of glucose and other nutrients, she can see how these nutrients are processed inside the embryo and map the metabolic pathways that drive early brain formation.  

The novelty of her research lies both in approach and perspective. Metabolism is the biological layer most closely linked to the environment, including nutrition. What we eat impacts metabolism long before affecting genes or proteins. Studying metabolism in vivo provides a more accurate view of the embryonic environment than cells grown in a dish, which cannot fully replicate these biological processes. 

The potential impact could be significant. A deeper understanding of metabolic instruction could help public health institutions provide clearer guidance for pregnant women. For example, how nutritional choices during pregnancy, such as high-fat diets or frequent consumption of sugar, may affect their child’s long-term brain health. While primarily mechanistic, these findings may also support future translational advances, ranging from investigations of metabolic targets in neurological disorders to studies examining the effects of IVF embryo culture conditions and their subsequent optimization, where minor metabolic changes may have lasting consequences. 

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