What about humans separating us from nonhuman primates, our closest living relatives? One of the biggest differentiators, from a scientific point of view, is the much larger size of our brain – and now, we have found a key secret behind this unparalleled growth.
In new research comparing different types of brain organoids – miniaturized masses of brain tissue grown from stem cells – scientists have discovered a key developmental difference in the development of neural stem cells between human brain tissue, gorilla and chimpanzee.
Neural stem cells (also called neuroepithelial cells) are a form of multipotent stem cells, giving rise to the neurons and glial cells that make up the central nervous system. But how this transition occurs during early brain development is not the same in all primates, new research shows.
As neuronal stem cells pass into certain types of brain cells, they change shape, which in turn affects the rate at which they can divide and eventually form neurons. In mice, such a shape change was known to occur in just a few hours, eventually limiting the amount of brain cells that animals produce.
(S.Benito-Kwiecinski / MRC LMB / Cell)
Above: neural stem cells every five days, with a different shape, less modified in humans (left) compared to monkeys (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, in fact, lasting several days. For gorillas and chimpanzees, the delayed change in shape gives them about five days to continue generating new neurons.
Human neuroepithelial cells last even longer until the transition – even a whole week, allowing the processes of neurogenesis to function longer, which in turn makes more brain cells, more brain tissue, and finally it creates larger brains (or, as seen here, larger organoids sit in a vessel).
“We found that a delayed change in the shape of cells in the early brain is enough to change the course of development, helping to determine the number of neurons that are made,” says developmental biologist LMB and lead researcher Madeline Lancaster.
“It is remarkable that a relatively simple evolutionary change in cell shape could have major consequences for the evolution of the brain.”
In addition to identifying the difference in transition, however, the analysis of organoids also revealed what makes developmental changes possible.
According to researchers, a gene called ZEB2 plays a central role in regulating the process, causing neural stem cells to change shape and mature earlier, which shortens the time they can proliferate before they become the progenitor cells that form in eventually in neurons. .
(S.Benito-Kwiecinski / MRC LMB / Cell)
Above: organoids of the human brain at the age of five weeks, substantially larger than the organoids of gorillas and chimpanzees (respectively from left to right).
Not only that, but in experiments in which the dynamics of ZEB2 expression were manipulated, the researchers showed that organoids could also be manipulated – with human brain organoids shrinking when the gene was improved and a gorilla organoid that more closely resembles brain volume. human 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 work exactly the same way in the real brains of human or non-human primates.
However, researchers say this is a huge clue as to what probably represents much of the brain size difference between humans and other large monkeys – and future studies, including experimenting with transgenic mice or imaging monkey embryos, would could shed an extra light. .
“This provides some of the first information about what’s different in the developing human brain that sets us apart from our closest relatives, the other great apes,” says Lancaster.
“I feel like I’ve really learned something fundamental about the questions that interest me for as long as I can remember – what makes us human.”
The findings are reported in Cell.