A new study is the first to identify how the human brain grows much more, with three times more neurons, compared to the brains of chimpanzees and gorillas. The study, led by researchers at the Molecular Biology Laboratory of the Medical Research Council (MRC) in Cambridge, UK, identified a key molecular switch that can make monkey brain organoises grow larger than humans, and vice versa.
The study, published in the journal Cell, compared “brain organoids” – three-dimensional tissue grown from stem cells that shape the early development of the brain – grown from human stem cells, gorillas and chimpanzees. Like real brains, the organoids of the human brain have grown much larger than the organoids of other monkeys.
Dr. Madeline Lancaster, of the Molecular Biology Laboratory of the MRC, who led the study, points out that “it provides a first look at what is different in the developing human brain, which differentiates us from our closest relatives. , the other big monkeys. the striking difference between us and other monkeys is how incredibly big our brains are, ”he adds.
In the early stages of brain development, neurons are produced by stem cells called neuronal progenitors. These progenitor cells initially have a cylindrical shape that facilitates their division into daughter cells identical to the same shape.
The more neuronal progenitor cells multiply in this phase, the more neurons will be later. And as the cells mature and slow down their multiplication, they elongate, forming a shape similar to that of a stretched ice cream cone.
Earlier, research in mice showed that their neuronal progenitor cells mature in a cone shape and slow down their multiplication in a few hours. Now, brain organoids have allowed researchers to discover how this development occurs in humans, gorillas and chimpanzees. They found that in gorillas and chimpanzees this transition takes a long time, as it lasts about five days.
The human parents were delayed in this transition, lasting about seven days. Human progenitor cells maintained their cylindrical shape longer than those of other monkeys and during this time they divided more frequently, producing more cells.
This difference in the rate of transition from neuronal progenitors to neurons means that human cells have more time to multiply. This could be largely responsible for about three times the number of neurons in the human brain compared to the brains of gorillas or chimpanzees.
Dr. Lancaster, who was part of the team that created the first brain organoids in 2013, points out that they found that “a delayed change in the shape of early brain cells is enough to change the course of development, helping to determine the number of neurons that are manufactured “.
“It’s surprising that a relatively simple evolutionary change in cell shape can have important consequences for brain evolution,” he said. “I feel like I’ve learned something fundamental about the questions that have interested me as long as I can remember: what makes us human.” “
To discover the genetic mechanism that determines these differences, the researchers compared the expression of genes – which genes are activated and deactivated – in the organoids of the human brain to other monkeys. They identified differences in a gene called “ZEB2,” which was activated earlier in gorilla organoids than in humans.
To test the effects of the gene on gorilla progenitor cells, they delayed the effects of ZEB2. This slowed the maturation of progenitor cells, causing the gorilla’s brain organoids to grow more like humans: slower and larger.
In contrast, the earlier onset of the ZEB2 gene in human progenitor cells promoted a premature transition in human organoids, so that they developed more than those in monkeys.
Researchers note that organoids are a model and, like all models, do not fully reproduce real brains, especially mature brain function. But for fundamental questions about our evolution, these brain tissues on a plate provide an unprecedented perspective on the key stages of brain development that would be impossible to study otherwise.