The new research is the first to identify how the human brain grows much larger, with three times as many neurons, as the chimpanzee and gorilla brains. A study led by researchers from the Molecular Biology Laboratory of the Medical Research Council (MRC) in Cambridge, UK, identified a key molecular switch that can make monkey organelles grow more like human organelles, and vice versa.
Study, published in the journal Cell, he compared “brain organoids” – 3D tissues grown from stem cells that model early brain development – that were grown from human, gorilla and chimpanzee stem cells.
Similar to the real brain, the organelles of the human brain have grown much larger than the organelles of other monkeys.
Dr Madeline Lancaster of the MRC’s Molecular Biology Laboratory, who led the study, said: “This provides the first insight into what is different in human brain development that sets us apart from our closest living relatives, other great apes. The most striking difference between us and other monkeys is how incredibly big our brains are. “
During the early stages of brain development, neurons produce stem cells called neural progenitors. These stem cells initially have a cylindrical shape that makes it easier for them to separate into identical daughters with the same shape.
The more neurons multiply at this stage, the more neurons there will be later.
As the cells mature and slow down their proliferation, they elongate, forming a shape like a stretched ice cream cone.
Previously, research on mice showed that their nerve stem cells mature into a conical shape and slow their proliferation by several hours.
Brain organelles have now enabled 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, occurring approximately five days.
Human offspring delayed this transition even further, taking about seven days. Human progenitor cells retained their cylinder-like shape longer than other apes and during that time they divided more frequently, creating more cells.
This difference in the rate of transition from neuronal progenitors to neurons means that human cells have more time to proliferate. This could be largely responsible for approximately three times the number of neurons in the human brain compared to the gorilla or chimpanzee brain.
Dr. Lancaster said: “We have found that a delayed change in the shape of cells in the early brain is enough to change the course of development, helping to determine the number of neurons created.
“It’s remarkable that a relatively simple evolutionary change in cell shape could have major implications for brain evolution. I feel like we’ve really learned something fundamental about issues that have interested me for as long as I can remember – what makes us human.”
To discover the genetic mechanism that drives these differences, the researchers compared gene expression – which genes are turned on and off – in the organelles of the human brain relative to other monkeys.
They found differences in a gene called ‘ZEB2’, which is involved in gorilla brain organoids rather than in human organoids.
To test the effects of genes in gorilla precursor cells, they delayed the effects of ZEB2. This slowed down the maturation of the progenitor cells, making the organelles of the gorilla’s brain develop more similarly to humans – slower and larger.
In contrast, the incorporation of the ZEB2 gene earlier into human genus cells promoted premature transition in human organoids, so that they evolved more like ape organoids.
The researchers note that organoids are a model and, like all models, do not have to fully replicate the real brain, especially the mature function of the brain. But for basic questions about our evolution, these brain tissues in food provide an unprecedented look at key stages of brain development that would otherwise be impossible to study.
Dr. Lancaster was part of the team that created the first brain organoids in 2013.
This study was funded by the Medical Research Council, the European Research Council and the UK Cancer Research.