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This is one of the defining attributes of humans: compared to our closest primate relatives, we have incredibly large brains.
Now, scientists have shed light on the reasons for the difference by collecting cells from humans, chimpanzees and gorillas and turning them into brain pieces in the lab.
Tests on tiny “brain organoids” reveal a so far unknown molecular switch that controls brain growth and makes the human organ three times the size of the brains of great apes.
Tinkering with the switch and the human brain loses its growth advantage, while the great ape brain can be made to develop more like a human’s.
“What we’re seeing is a difference in cellular behavior very, very early on, which allows the human brain to grow bigger,” said Dr Madeleine Lancaster, a developmental biologist at the Medical Research Council’s Molecular Biology Laboratory in Cambridge. “We are able to account for almost all of the size difference.”
The healthy human brain typically grows to around 1,500 cc in adulthood, which is about three times the size of the brain of a 500 cc gorilla or the brain of a 400 cc chimpanzee. But figuring out why has been very difficult, not least because brain development in humans and great apes cannot be easily studied.
In an effort to understand the process, Lancaster and his colleagues collected cells, often left behind by tests or medical operations, from humans, gorillas and chimpanzees, and reprogrammed them into stem cells. They then developed these cells in a way that encouraged them to turn into brain organoids – small pieces of brain tissue a few millimeters wide.
After several weeks, the human brain organoids were by far the biggest of the lot, and close examination revealed why. In human brain tissue, the so-called neural progenitor cells – which make up all brain cells – divide more than those in the brain tissue of great apes.
Lancaster, whose study is published in Cell, added: “You have an increase in the number of these cells, so once they go into making different brain cells, including neurons, you have more to go. start, so you get an increase in the whole population of brain cells throughout the cortex. “
Mathematical modeling of the process has shown that the difference in cell proliferation occurs so early in brain development that it ultimately leads to a nearly doubling of the number of neurons in the adult human cerebral cortex compared to that of great apes. .
The researchers then identified a crucial gene for the process. Known as Zeb2, it later turns on in human tissue, allowing cells to divide further before they mature. Tests have shown that delaying the effects of Zeb2 causes gorilla brain tissue to grow larger, while activating it earlier in human brain organoids causes them to grow more like those of monkeys.
John Mason, professor of molecular neural development at the University of Edinburgh, who was not involved in the research, said it highlights the power of organoids to study brain development.
“It’s important to understand how the brain develops normally, partly because it helps us understand what makes humans unique and partly because it can give us important information about how neurodevelopmental disorders can. occur, ”he said.
“Brain size can be affected in certain neurodevelopmental disorders, for example macrocephaly is a hallmark of certain autism spectrum disorders, so understanding these very basic processes of embryonic brain development could lead to a better understanding of these disorders. “, he added.
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