Somewhere in a Dresden laboratory, small three-dimensional clusters of developing brain tissue, grown from stem cells of humans, chimpanzees and gorillas, have offered a quiet hint about one of the oldest questions people ask about themselves. The hint is that the human neocortex may owe part of its distinctiveness not to genes found nowhere else, but to the same shared genetic toolkit being tuned differently. The work, reported in Nature Communications by a team led from TUD Dresden University of Technology, traces this tuning to the shape of the cells that build the cortex, a shape that earl
Human Brain Cells May Differ From Apes' in Gene Settings, Not Gene Lists
Largely the same toolkit as apes, just with different settings
Mark
So what did they actually find? Different genes, or something else?
Mimi
Something else. Human and ape genomes are nearly identical, and the team looked at the regulatory DNA that sets how strongly genes run. They found 599 regions more accessible in human basal radial glia than in ape cells.
Mark
Those are the neural stem cells that build the neocortex?
Mimi
Progenitors involved in building it, yes. Many of the regions were tied to genes that shape cells and their extensions.
Luke
Careful with the 599, though. Accessibility flags a region as potentially active. It doesn't make each one a proven cause of anything.
Mark
Fair. So how did they move past comparison?
Mimi
They disrupted two genes, FAM107A and CNGA3, in human organoids with CRISPR-Cas9. Both reduced the share of cells with complex shapes.
Luke
But not equally. FAM107A cut the extensions off the cell body and lowered neuron numbers. CNGA3 didn't significantly change the individual measurements. Calling both simply branching genes would be wrong.
Mark
And the chimpanzee experiment?
Mimi
Raising human FAM107A in chimp organoids produced an effect like disrupting it in human ones. So the level matters, not just more or less.
Luke
And what's still unknown is the whole chain, from each DNA switch to gene activity to cell behavior to actual neocortex expansion. This study doesn't close that, and organoids can't speak to intelligence or adult brain size.
Der Puls
- Researchers found 599 DNA regions more open in human progenitor cells than in ape cells, a striking list that still awaits proof of what each region actually does.
- Disrupting the gene FAM107A in human organoids flattened the complex cell shapes of progenitors and reduced neuron numbers, pushing the study into the territory of cause and consequence.
- Knocking out CNGA3 left the measured structures largely unchanged, a reminder that not every candidate gene carries the weight its neighbors seem to suggest.
- Raising human FAM107A in chimpanzee organoids reproduced the effect of disruption, suggesting the level of expression matters as much as the direction of change.
- The team's next step is to connect regulatory regions to their target genes and to real neuron production, because the explanation for neocortex expansion remains unfinished.
Somewhere in a Dresden laboratory, small three-dimensional clusters of developing brain tissue, grown from stem cells of humans, chimpanzees and gorillas, have offered a quiet hint about one of the oldest questions people ask about themselves. The hint is that the human neocortex may owe part of its distinctiveness not to genes found nowhere else, but to the same shared genetic toolkit being tuned differently. The work, reported in Nature Communications by a team led from TUD Dresden University of Technology, traces this tuning to the shape of the cells that build the cortex, a shape that earlier research has linked to how many neurons a developing brain can produce.
In Dresden, researchers grew miniature models of developing brain tissue from stem cells of humans, chimpanzees and gorillas, and compared how the earliest cells of the neocortex behaved. The neocortex supports speech, abstract thought and long-term planning, though these experiments measured none of those abilities directly. The team, led by Mareike Albert, chose organoids because developing brain tissue from great apes is not available for research, and the ethical reasons for that are good ones.
Focusing on basal radial glia, progenitor cells that help build the neocortex, the researchers identified 599 short DNA regions that were more accessible in human cells than in ape cells. Accessibility suggests a region may be active; it does not prove it drives brain growth. Many of these regions sat near genes that shape cell bodies and their extensions, which matters because earlier studies linked more elaborate progenitor shapes to greater capacity for making neurons.
Testing two candidates, FAM107A and CNGA3, the team disrupted each in human organoids. Both reduced the share of complex-shaped progenitors, but only FAM107A also reduced the number of extensions and the neurons produced. A further twist came when raising human FAM107A in chimpanzee organoids produced an effect resembling disruption, hinting that getting the level right matters as much as the direction of change.
Albert's broader reading is that humans may rely on largely the same toolkit as apes, set differently. The authors are clear about the limits: organoids capture selected developmental features, not whole living brains, and they cannot settle adult brain size, intelligence or evolutionary history. The real work ahead is linking those 599 regions to their target genes and to the neurons they help create.
In a Dresden laboratory, researchers grew small three-dimensional models of developing brain tissue from stem cells of three species: humans, chimpanzees and gorillas. Then they compared how the earliest cells of the neocortex behaved. The result, published in Nature Communications, points to a possibility that is easy to state and hard to prove: the human brain may owe part of its character less to unique genes than to how familiar genes are turned up or down.
The study was led by Mareike Albert at TUD Dresden University of Technology, who heads a group at the Center for Regenerative Therapies. The neocortex supports speech, abstract thinking and long-term planning, though the experiments did not measure any of those abilities. Albert's reasoning for using organoids is practical. Differences in brain size arise during development, when most neurons are generated, but developing brain tissue from great apes is not available for research, for good ethical reasons.
The team focused on basal radial glia, neural progenitor cells that help build the neocortex. They identified 599 candidate regulatory regions of DNA that were more accessible in human basal radial glia than in the matching ape cells. Theresa M. Schütze, who led the experimental work, described such regions as short DNA sequences that act like dimmers, turning gene activity up or down. Accessibility marks a region as potentially active, so the list is not 599 proven causes of brain enlargement.
Many of the highlighted regions were linked to genes that shape cells and their extensions. That matters because earlier work tied more elaborate progenitor shapes to a greater capacity to produce neurons. A 2019 study in Cell Stem Cell connected the number of extensions to progenitor proliferation, and found that raising levels of the protein PALMDELPHIN promoted extensions and proliferation in mouse and ferret tissue, while disrupting its gene in human fetal tissue reduced both. One proposed explanation is that more elaborate cells reach more growth-promoting signals in their surroundings.
The Dresden team went on to test two genes, FAM107A and CNGA3, in human organoids. Using CRISPR-Cas9, they disrupted each separately. Both reduced the proportion of basal radial glia with complex shapes. The details diverged, though. Disrupting FAM107A reduced the number of extensions growing directly from the cell body, and it also reduced neuron numbers in the examined organoid regions. Disrupting CNGA3 did not significantly change the individual structural measurements the team examined.
A further experiment complicated any simple story of more being better. When the researchers raised human FAM107A expression in chimpanzee organoids, the structural effect resembled what happened when the gene was disrupted in human organoids. The authors read this as evidence that the right level of expression matters, not just its direction.
Albert summarized the broader idea this way: it is not necessarily different genes that make a human brain special; humans use largely the same toolkit as apes, with different settings. The study also sits among earlier organoid work, including a 2021 study in Cell showing that delaying an early cell-shape transition in human organoids was associated with larger models.
The limits are plain. Organoids reproduce selected features of development, not whole brains growing in living animals, and these results cannot directly establish adult brain size, intelligence or the evolutionary history of a species. The next task is to link candidate DNA regions to their target genes and to the cell behavior and neuron production that follow, rather than treating the list of 599 as a finished explanation.
Bemerkenswerte Zitate
It is not necessarily different genes that make a human brain special; we use largely the same toolkit as apes, just with different settings.— Mareike Albert, TUD Dresden University of Technology
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