The human brain is three times the size of our closest primate relatives and a new study is the first to identify how we developed the larger cerebrum.
Researchers at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge solved the mystery by collecting cells from humans, gorillas and chimpanzees that were reprogrammed into stem cells to grow ‘brain organoids’ – which are tiny developing brains.
During the early development, neural progenitor cells divide to create brain cells and the test showed more divided in the human tissue that the other specimens.
These progenitor cells begin as a cylindrical shape to easily split into identical daughter cells with the same shape – and the more they multiply, the more neurons will form later.
As the brain organoids grew, the human progenitor cells maintained their cylinder-like shape longer than other apes and during this time they split more frequently, producing more cells.
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Scientists collecting cells from humans, gorillas and chimpanzees that were reprogrammed into stem cells to grow ‘brain organoids’ – which are tiny developing brains. As the brain organoids matured, the team spotted a previously unknown molecular switch that controls growth
Dr Madeline Lancaster, from the MRC Laboratory of Molecular Biology, who led the study, said: ‘This provides some of the first insight into what is different about the developing human brain that sets us apart from our closest living relatives, the other great apes.
‘The most striking difference between us and other apes is just how incredibly big our brains are.’
To uncover the genetic mechanism driving these differences, the researchers compared gene expression – which genes are turned on and off – in the human brain organoids versus the other apes.
They identified differences in a gene called ‘ZEB2’, which was turned on sooner in gorilla brain organoids than in the human organoids.
During the early development, neural progenitor cells divide to create brain cells and the test showed more divided in the human tissue that the other specimens. These progenitor cells begin as a cylindrical shape to easily split into identical daughter cells with the same shape – and the more they multiply, the more neurons will form later.
To test the effects of the gene in gorilla progenitor cells, they delayed the effects of ZEB2.
This slowed the maturation of the progenitor cells, making the gorilla brain organoids develop more similarly to human -slower and larger.
Conversely, turning on the ZEB2 gene sooner in human progenitor cells promoted premature transition in human organoids, so that they developed more like ape organoids.
The average human brain weighs about three pounds, while a gorilla’s is one-pound and a chimpanzee’s clock in at 15 ounces.
Although scientists have known humans have larger brains, how the difference emerged during evolution remained a mystery.
Lancaster and her team embarked on this work by collecting human, gorilla and chimpanzee cells from medical tests and operations and transformed them into stem cells.
This allowed them to grow brain tissue in the lab to study the early development of the organ.
In several weeks, the human brain organoids had grown much larger than the other two specimens.
During the early stages of brain development, neurons are made by stem cells called neural progenitors.
These progenitor cells initially have a cylindrical shape that makes it easy for them to split 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 later.
As the cells mature and slow their multiplication, they elongate, forming a shape like a stretched ice-cream cone.
As the brain organoids grew, the human progenitor cells maintained their cylinder-like shape longer than other apes and during this time they split more frequently, producing more cells
Previous research was conducted in mice, which showed this process happens within a few hours and concludes that the longer the process, the larger the brain.
However, the new study found that this transition takes longer in gorillas and chimpanzees – approximately five days.
Human progenitors were even more delayed in this transition, taking around seven days.
The human progenitor cells maintained their cylinder-like shape for longer than other apes and during this time they split more frequently, producing more cells.
This difference in the speed of transition from neural progenitors to neurons means that the human cells have more time to multiply.
This could be largely responsible for the approximately three-fold greater number of neurons in human brains compared with gorilla or chimpanzee brains.
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 determine the numbers of neurons that are made.
‘It’s remarkable that a relatively simple evolutionary change in cell shape could have major consequences in brain evolution,’ said Lancaster.
‘I feel like we’ve really learnt something fundamental about the questions I’ve been interested in for as long as I can remember — what makes us human.’