New techniques reveal previously unseen communication between living systems in the body of a zebrafish. And yes, that glowing node between its eyes is the pineal gland.
(Ruetten et al., Nature, 2026)
It's easy to miss important connections depending on how you look at an organism. Microscopes show us the fine details of a body, dissection has helped us identify different organs, and X-rays can show us the bigger picture of internal systems.
But until now, it's been tricky to see how living cells communicate across those systems, which traditionally have been studied in isolation, even though our bodies ultimately work as a whole.
Now, scientists have figured out how to watch cells from disparate parts of the body communicate with each other. Their research has been presented in the journal Nature.
https://www.youtube.com/watch?v=NuuwV6LitjU
"This work bridges two fundamental scales of biology – the cell and the organism – such that we can now fill that observability gap," says computational neuroscientist Virginie Ruetten, who developed the technique along with a team based at the Howard Hughes Medical Institute in the US.
"There are some really basic properties that were just missing because it's been very difficult to look at cellular responses at scale."
The new imaging technique – dubbed WHOLISTIC (WHole-Organism Live-Imaging System for recording Tissue and IntraCellular activity) – captures cellular activity across the entire body, second by second.
So far, Ruetten and team have used this technique to image real-time signaling in naturally transparent animals: first with larval zebrafish, and then with another kind of freshwater fish, Danionella cerebrum, which remain transparent into adulthood.
https://www.youtube.com/watch?v=XXk5KxhS5_c
Both of these fish are important model organisms in scientific research.
Being able to see how the cells in their bodies communicate across different organ systems could help scientists figure out how similar systems in our own bodies might be working, too.
Calcium is a near-universal signal cells use to communicate with each other. It's involved in all manner of biological processes. It helps muscles to contract and synapses to fire; it's crucial at the start of life, when sex cells are fertilized, and at the end, when cells are programmed for death.
The WHOLISTIC technique uses genetic engineering to make nearly every cell in the body express fluorescent calcium sensors. These sensors literally light up when calcium levels in the cells shift.
A single fluorescence channel enables identification of organs and tissues via distinct visual textures. The areas with a yellow 'glow' show stronger fluorescence from the calcium sensor.
(Ruetten et al., Nature, 2026)
"This now allows all these fields – physiology, neuroscience, behavior, cell biology – to connect and study all of them in the same animal."
This whole-body imaging approach has already led to some unexpected findings.
For one, the scientists saw calcium sensors in a fish's chondrocytes (the main cells that form cartilage) flaring up in response to the cold.
They were also surprised to see the brain's protective tissue layers (meninges) – not just its neurons – responding to ketamine.
Zooming out, the body's rhythms were illuminated like never before.
"At the multi-organ scale, it revealed unknown muscle synergies and muscle–organ interactions," the authors report in their paper.
"At the whole-organism scale, the method captured brainstem-controlled redistribution of body-wide blood flow."
The team hopes that scientists around the world will be able to adopt this method for their own research, offering unprecedented insight into the body as a whole.
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