A new study is the first to identify how the human brain grows much larger, with three times the number of neurons, compared to chimpanzees and gorilla brains. The study, led by researchers at the Medical Research Council (MRC) Laboratory for Molecular Biology, in Cambridge, UK, identified an important molecular switch that can cause monkeys’ brain organoids to grow larger like humans, and vice versa.
The study, published in the journal Cell, compared “brain organoids” – three-dimensional tissues grown from stem cells that model early brain development – grown from stem cells from humans, gorillas and chimpanzees. Like real brains, the organoids of the human brain grew much larger than the organoids of other apes.
Dr. Madeline Lancaster, of MRC’s Molecular Biology Laboratory, who led the study, emphasizes that “this provides a first glimpse of what is different in the evolving human brain that sets us apart from our closest living relatives, the other great apes. A striking difference. between us and other monkeys is how incredibly big our brains are, ”he adds.
During the early stages of brain development, neurons are produced by stem cells called neural precursors. These progenitor cells initially have a cylindrical shape that facilitates their division into identical daughter cells of the same shape.
The more times the neural progenitor cells multiply in this phase, the more neurons there will be later. And as cells mature and slow their multiplication, they lengthen and form a shape similar to that of a stretched ice cream cone.
Previously, research in mice had shown that their neuronal progenitor cells mature conically and slow their multiplication within hours. Now brain organoids have enabled researchers to discover how this development takes place in humans, gorillas and chimpanzees. They found that in gorillas and chimpanzees, this transition takes a long time, as it takes about five days.
Human parents were further delayed in this transition, which took about seven days. Human progenitor cells retained their cylindrical shape longer than other monkeys and during this time they divided more often, producing more cells.
This difference in speed of transition from neural precursors to neurons means that human cells have more time to multiply. This could be largely responsible for roughly three times the number of neurons in the human brain compared to gorilla or chimpanzee brains.
Dr. Lancaster, who was part of the team that created the first brain organoids in 2013, emphasizes that they have found that “ a delayed change in the shape of cells in the early brain is enough to alter the course of development and help determine the number of neurons produced. “.
“It is surprising that a relatively simple evolutionary change in the shape of cells can have important implications for brain evolution,” he continues. “I feel like we have learned something fundamental about the questions that have interested me for so long. I remember what makes us human.”
To discover the genetic mechanism behind these differences, the researchers compared gene expression – which genes are turned on and off – in organoids of the human brain with other monkeys. They identified differences in a gene called “ZEB2,” which was activated earlier in gorilla brain organoids than in humans.
To test the gene’s effects on gorilla progenitor cells, they slowed down the effects of ZEB2. This slowed progenitor cell maturation, causing gorilla brain organoids to develop more like humans: slower and larger.
In contrast, turning on the ZEB2 gene earlier in human progenitor cells promoted premature transition in human organoids so that they evolved more like those in monkeys.
The researchers note that organoids are a model and, like all models, do not fully reproduce real brains, especially adult brain function. But for fundamental questions about our evolution, these brain tissues on a plate provide unprecedented insight into key stages of brain development that would otherwise be impossible to study.