What about humans separating us from nonhuman primates, our closest living relatives? Scientifically, one of the biggest differentiators is the size of our much larger brains, and we have now found a key secret behind this unparalleled growth.
In a new study comparing different types of brain organoids, miniaturized masses of brain tissue from stem cells, scientists found a key difference in the development of neuronal stem cell development between human brain tissue, gorilla · the i chimpanzee.
Neuronal stem cells (also called neuroepithelial cells) are a form of multipotent stem cell, which gives rise to the neurons and glial cells that form the central nervous system. But the way this transition occurs during early brain development is not the same in all primates, new research shows.
As neuronal stem cells move to specific types of brain cells, they change their shape, which in turn affects the rate at which neurons can divide and eventually form. In mice, this shape change was known to occur in a matter of hours, eventually limiting the amount of brain cells the animals produce.
(S.Benito-Kwiecinski / MRC LMB / Cell)
Above: neuronal stem cells at five days, with a different and less altered shape in humans (left) compared to apes (right).
Now, scientists at the Molecular Biology Laboratory (LMB) of the UK Medical Research Council have shown that the process takes much longer in primates and in fact takes several days. For gorillas and chimpanzees, the delayed shape change gives them about five days to continue generating new neurons.
Human neuroepithelial cells take even longer to transition, even for an entire week, allowing the processes of neurogenesis to work for longer, which in turn leads to more brain cells, more brain tissue, and more. , ultimately produce larger brains (or, as seen here, larger sitting organoids) on a plate).
“We have found that a delayed change in the shape of initial brain cells is enough to change the course of development, helping to determine the number of neurons that are produced,” explains LMB developmental biologist and lead researcher Madeline Lancaster.
“It is notable that a relatively simple evolutionary change in the shape of cells can have important consequences on the evolution of the brain.”
But in addition to identifying the transition difference, analysis of organoids has also revealed what makes developmental changes possible.
According to the researchers, a gene called ZEB2 plays a central role in regulating the process, causing neuronal stem cells to change shape and effectively mature sooner, which reduces the time they can proliferate before they become progenitor cells that end up forming in neurons. .
(S.Benito-Kwiecinski / MRC LMB / Cell)
At the top: organoids of the human brain at five weeks of age, substantially larger than the organoids of gorillas and chimpanzees (from left to right, respectively).
Not only that, but in experiments in which ZEB2 expression dynamics were manipulated, the researchers showed that organoids could also be manipulated, with organoids in the human brain getting smaller as the gene and an organoid improved. of gorilla that most closely resembled the volume of human brain tissue when ZEB2 was inhibited.
The researchers point out that organoid tissue is never a perfect representation of real animal organs, so we cannot conclude that ZEB2 activity and inactivity would function in exactly the same way in real brains of human or non-human primates.
However, researchers say this is a huge clue about what probably explains much of the difference in brain size between humans and other great apes, and future studies, including experimenting with GMO mice or imaging. of ape embryos, they could shed even more light. .
“This provides some of the first insights into what’s different in the developing human brain that sets us apart from our closest living relatives, the other great apes,” Lancaster says.
“It seems to me that we’ve really learned something fundamental about the issues that have interested me since I can remember: what makes us human.”
The findings are reported in Cell.