What is it about humans that separate us from non-human primates, our closest relatives? One of the biggest differentiators, scientifically speaking, is the size of our much larger brains – and now we’ve uncovered a key secret behind that unparalleled growth.
In new research comparing different types of brain organoids – miniaturized masses of brain tissue grown from stem cells – scientists discovered a significant developmental difference in neural stem cell development between brain tissue from humans, gorillas and chimpanzees.
Neural stem cells (also called neuroepithelial cells) are a form of multipotent stem cells, which give rise to the neurons and glial cells that make up the central nervous system. But the way this transition occurs during early brain development isn’t the same in all primates, new research shows.
As neural stem cells transform into specific brain cell types, they change shape, which in turn affects the speed at which they can divide and eventually form neurons. In mice, such a shape change was known to occur within hours, ultimately limiting the amount of brain cells that the animals produce.
(S. Benito-Kwiecinski / MRC LMB / Cell)
Above: neural stem cells after five days, with a different, less altered shape in humans (left) compared to monkeys (right).
Now, scientists at the UK Medical Research Council’s Laboratory of Molecular Biology (LMB) have shown that in primates the process takes considerably longer, in fact several days. For gorillas and chimpanzees, the delayed shape change gives them about five days to generate new neurons.
Human neuroepithelial cells take even more time to switch – even a whole week, which allows neurogenesis processes to take longer, which in turn makes more brain cells, more brain tissue, and ultimately, bigger brains (or, as seen here , larger organoids that are contained in a bowl).
“We have found that a delayed change in the shape of cells in the early brain is enough to alter the developmental pathway, thereby determining the number of neurons produced,” explains LMB developmental biologist and lead researcher Madeline Lancaster.
“It is remarkable that a relatively simple evolutionary change in cell shape can have major implications for brain evolution.”
However, in addition to identifying the difference in transition, analysis of the organoids has also revealed what makes the developmental changes possible.
According to the researchers, a gene called ZEB2 plays a central role in regulating the process, causing the neural stem cells to change shape and mature earlier, shortening the time they can multiply before they become the progenitor cells that eventually form into neurons. .
(S. Benito-Kwiecinski / MRC LMB / Cell)
Above: five-week-old human brain organoids, significantly larger than gorilla and chimpanzee organoids (left to right, respectively).
Not only that, but in experiments manipulating the expression dynamics of ZEB2, the researchers showed that the organoids could also be manipulated – with human brain organoids getting smaller when the gene was amplified, making a gorilla organoid more like it. volume of the human brain. tissue when ZEB2 was inhibited.
The researchers emphasize that organoid tissue is never a perfect representation of actual animal organs, so we cannot conclude that ZEB2 activity and inactivity would function in exactly the same way in real human or non-human primate brains.
Nonetheless, the researchers say this is a huge clue to what likely explains much of the difference in brain size between humans and other great apes – and future studies, including experiments on transgenic mice or imaging monkey embryos, could shed even more light. .
“This provides one of the first insights into what’s different about the evolving human brain that sets us apart from our closest relatives, the other great apes,” says Lancaster.
“I feel like we’ve really learned something fundamental about the questions I’ve been interested in for as long as I can remember – what makes us human.”
The findings are reported in Cell