It’s one of the defining traits of being human: 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 blocks in the lab.
Tests on the tiny ‘brain organoids’ reveal a hitherto unknown molecular switch that controls brain growth and makes the human organ three times the size of the brain in apes.
If you tinker with the switch, the human brain loses its growth advantage, while the apes’ brain can be made to grow more like a human’s.
“What we are seeing very, very early is a difference in cellular behavior that allows the human brain to grow larger,” said Dr. Madeleine Lancaster, developmental biologist at the Molecular Biology Laboratory of the Medical Research Council in Cambridge. “We are able to explain almost all size differences.”
The healthy human brain typically reaches about 1500 cc in adulthood, about three times the size of the 500 cc gorilla brain or the 400 cc chimpanzee brain. But figuring out why is so difficult, not least because the brains of humans and great apes cannot be easily studied.
In an effort to understand the process, Lancaster and her colleagues collected cells, often left over from medical tests or surgery, from humans, gorillas and chimpanzees, and reprogrammed them into stem cells. They then grew these cells in such a way that they were encouraged to turn into brain organoids – tiny chunks of brain tissue a few millimeters wide.
After several weeks, the human brain organoids were by far the largest of the lot, and close research revealed why. In human brain tissue, so-called neural progenitor cells – which make up all cells in the brain – are more distributed than those in great apes’ brain tissue.
Lancaster, whose study is published in Cell, added, “You have an increase in the number of those cells, so once they switch to making the different brain cells, including neurons, you have more to begin with, so you gets an increase in the entire population of brain cells throughout the cortex. “
Mathematical modeling of the process showed that the difference in cell proliferation occurs so early in brain development that it ultimately leads to an almost doubling of the number of neurons in the adult human cerebral cortex compared to that in the great apes.
The researchers went on to identify a gene crucial to the process. Known as Zeb2, it turns on later in human tissue, allowing the cells to divide more before maturing. Tests showed that slowing down the effects of Zeb2 caused gorilla brain tissue to grow larger, while turning human brain organoids on earlier made them look more like the monkey.
John Mason, a professor of molecular neural development at the University of Edinburgh, who was not involved in the research, said it emphasized the power of organoids to study brain development.
“It is important to understand how the brain develops normally, partly because it helps us understand what makes people unique and partly because it can give us important insights into how neurodevelopmental disorders can arise,” he said.
“Brain size may be affected in some neurodevelopmental disorders, for example macrocephaly is a hallmark of some autism spectrum disorders, so understanding these very basic processes of embryonic brain development could lead to a better understanding of such disorders,” he added.