Illustration of zebrafish ©Gioele La Manno (EPFL)
Researchers at EPFL have created the first 4D lipid atlas of vertebrate development, revealing how fats shape our bodies from embryo to organism.
We often think of embryonic development as a genetic ballet, choreographed entirely by DNA and proteins. But there's another cast member quietly shaping the scene: lipids. These fat molecules aren't just fuel; they play structural, signaling, and even patterning roles as embryos develop.
Despite advances in genomics, we still don't fully understand how metabolism is arranged in different parts of the body during development. A big part of the metabolism puzzle are lipids, which vary widely in structure and function, and have been notoriously hard to map across entire organisms both in high resolution and across time.
Previous techniques only offered fragmented snapshots, but without a detailed atlas, scientists can't track where and when specific lipids appear in the developing body. This has limited our ability to understand not just basic biology, but also how metabolic disorders or congenital diseases might take root.
A team of researchers at EPFL have developed a new computational method which allowed them to build the first 4D lipid map of a vertebrate embryo-specifically, the zebrafish. "4D" refers to mapping lipids in the three dimensions of space plus the fourth dimension of time, which captures how lipid distributions change as the embryo develops. Using an innovative combination of imaging mass spectrometry and a new computational framework called uMAIA, they tracked over 100 lipid types across space and time.
The research was led by Professors Gioele La Manno, head of the Laboratory of Brain Development and Biological Data Science, and Giovanni D'Angelo, head of the The Kristian Gerhard Jebsen Foundation Chair in Nutrition and Metabolism, working with the Segmentation Timing and Dynamics Laboratory of Andrew Oates. It is published in Nature Methods.
A baseline for comparison
The team found that lipids form highly organized patterns that match anatomical structures. For example, certain sphingolipids - which are important for cell membranes and signaling - accumulated in the swim bladder, a fish organ that is analogous to human lungs. Others concentrated in developing brain regions or bone-forming areas. These spatial patterns suggest lipids play key roles in shaping organ function and identity.
Knowing where and when lipids appear can help researchers understand developmental diseases, like congenital metabolic disorders. It could also inform regenerative medicine or tissue engineering. And because lipid metabolism is often disrupted in diseases like cancer or Alzheimer's, this atlas offers a baseline for comparison.
"From this effort emerges not only a powerful resource but a Swiss army knife for doing this kind of mapping again and again across other system in health and disease," says Gioele La Manno.
