It’s one of the defining features of a human being: When compared to our closest major relatives, we have incredibly large brains.
Scientists are now shedding light on the reasons for the difference, by collecting cells from humans, chimpanzees and gorillas and turning them into brain clumps in the laboratory.
Tests on tiny “brain organelles” reveal a hitherto unknown molecular switch that controls brain development and makes the human organ three times larger than the brains of great apes.
Tampering with the key and the human brain losing its growth feature, while the great ape brain could be made to grow more like a human brain.
“What we’re seeing is a difference in cellular behavior very early on, which allows the human brain to grow larger,” said Dr. Madeline Lancaster, a developmental biologist at the Molecular Biology Laboratory of the Medical Research Council in Cambridge. “We are able to calculate nearly all the size difference.”
A healthy human brain is usually around 1500 cm long3 In adulthood, it is almost three times the size of 500 cm3 Gorilla brain or 400 cm3 The brain of a chimpanzee. But figuring out the reason for the difficulty, not least because the development of the brains of humans and great primates cannot be easily studied.
In an effort to understand the process, Lancaster and her colleagues collected cells, often left over from tests or medical processes, from humans, gorillas and chimpanzees, and reprogrammed them into stem cells. Then they grew these cells in a way that encouraged them to transform into brain organelles – small clumps of brain tissue a few millimeters wide.
After several weeks, the organelles of the human brain were by far the largest, and a closer examination revealed the cause. In human brain tissue, so-called neurogenic progenitor cells – which continue to make up all cells in the brain – divide more than those in great ape brain tissue.
Lancaster, who was studying Posted in the cell“You have an increase in the number of these cells, so once you turn to making different brain cells, including neurons, you have more to start with, until you get an increase in the total brain cells across the entire cortex.”
Mathematical modeling of the process showed that variation in cell proliferation occurs very early in brain development, ultimately resulting in a doubling of the number of neurons in the cerebral cortex of an adult compared to those in great apes.
The researchers went on to identify a gene that is critical in this process. Known as Zeb2, it is later turned on in human tissues, allowing cells to divide further before they mature. Tests have shown that delaying the effects of Zeb2 made gorilla brain tissue grow larger, while turning it on early in human brain organelles made them grow like apes.
John Mason, a professor of molecular neurodevelopment at the University of Edinburgh who was not involved in the research, said he shed light on the power of organelles in the study of brain development.
He said: “It is 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 insights into how neurodevelopment disorders arise.”
He added, “Brain size can be affected in some neurodevelopmental disorders. For example, enlargement of the head is a feature of some autism spectrum disorders, so understanding these very basic processes of fetal brain development can lead to a better understanding of these disorders.”