A new study is the first to identify how human brains grow much more, with three times as many 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 could cause apes’ brain organoids to grow more like humans. , and vice versa.
The study, published in the journal Cell, compared “brain organoids” – three-dimensional tissues grown from stem cells that shape early brain development – grown from stem cells. human, gorilla and chimpanzee. Like real brains, human brain organoids grew much larger than the organoids of other apes.
Dr. Madeline Lancaster, of the Molecular Biology Laboratory at the MRC, who led the study, points out that “this provides a first glimpse of what is different in the developing human brain that differentiates us from our closest living relatives “The other big apes. The most striking difference between us and the other apes is how incredibly big our brains are,” he adds.
During the early stages of brain development, neurons are produced by stem cells called neural progenitors. These progenitor cells initially have a cylindrical shape that facilitates their division into identical daughter cells with the same shape.
The more times the neural progenitor cells multiply at this stage, the more neurons there will be afterwards. And as the cells mature and slow their multiplication, they elongate, forming a shape similar to that of a stretched ice cream cone.
Earlier, research in mice had shown that their neuronal progenitor cells mature in a cone shape and slow their multiplication in a matter of 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 occurs in about five days.
Human progenitors were further delayed in this transition, taking about seven days. Human progenitor cells maintained their cylindrical shape for longer than those of other apes and during this time they divided more frequently, producing more cells.
This difference in the rate of transition from neural progenitors to neurons means that human cells have more time to multiply. This could be largely responsible for the approximately three times greater number of neurons in human brains 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 have found that “a delayed change in the shape of cells in the brain early is enough to change the course of development, helping to determine the number of neurons that are manufactured “.
“It’s amazing that a relatively simple evolutionary change in the shape of cells can have important consequences for the evolution of the brain,” he said. “I feel we’ve learned something fundamental about the issues that have interested me since I use reason: what makes us human. “
To discover the genetic mechanism that drives these differences, the researchers compared gene expression – which genes are activated and deactivated – in human brain organoids to other apes. They identified differences in a gene called “ZEB2”, which was activated earlier in the brain organoids of gorillas than in humans.
To test for the effects of the gene on gorilla progenitor cells, they delayed the effects of ZEB2. This slowed the maturation of the progenitor cells, causing the gorilla’s brain organoids to develop more similarly to humans: more slowly and larger.
In contrast, earlier activation of the ZEB2 gene in human progenitor cells promoted a premature transition in human organoids, so that they developed more similarly to apes.
Researchers point out that organoids are a model and, like all models, do not completely reproduce real brains, especially mature brain function. But for fundamental questions about our evolution, these brain tissues in a plaque provide an unprecedented view of key stages of brain development that would be impossible to study otherwise.