The human brain is much larger than the brain of our closest living relative, the chimpanzee. Evolutionary speaking, this dramatic difference can be traced to the moment when humans diverged from a common ancestor shared with chimpanzees and other great apes. And from a molecular standpoint, a new study shows how exactly the human brain grows so large during its development.

Researchers at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK, harvested cells from humans, gorillas, and chimps, and reprogrammed them into stem cells. These stem cells were later coaxed to grow into ‘brain organoids’ — which are basically tiny developing brains.

While doing so, it became immediately clear that human brain organoids grew a lot larger than those of other apes, just like how our adult brains can grow a lot bigger. An adult human brain typically reaches about  1,500cm³ in volume, whereas the brains of gorillas and chimps have an average volume of just 500cm³ and 400cm³, respectively.

“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,” said Dr. Madeline Lancaster, from the MRC Laboratory of Molecular Biology, who led the study.

Neurons grow from a type of stem cell called a neural progenitor. Initially, these progenitor cells have a cylindrical shape that facilitates their division into identical daughter cells with the same shape. The more of these neural progenitor cells there are that multiply at this critical stage, the more neurons the brain will have once development is complete. When the progenitor cells mature, their multiplication slows down dramatically and their shape morphs into a shape resembling a stretched ice-cream cone.

In gorillas and chimps, this transition takes a long time, occurring over five days. Human progenitors were even more delayed in this transition, taking around seven days. The difference can add substantially in terms of brain volume because there are more neuron cells that multiply. About half of the size difference between the brains of humans and great apes can be accounted for by this cellular behavior.

The process is mediated by a crucial gene known as Zeb2, which is switched on later in human tissue. In experiments, the researchers tweaked the Zeb2 gene in gorilla brain tissue, causing it to grow larger. Turning the gene on sooner in human brain organoids made them grow the size of apes.

Brain size can be affected by some neurodevelopmental disorders, so gaining insight into the cellular mechanisms of early brain development may lead to novel treatments.

“It’s remarkable that a relatively simple evolutionary change in cell shape could have major consequences in brain evolution. I feel like we’ve really learned something fundamental about the questions I’ve been interested in for as long as I can remember—what makes us human,” said Dr. Lancaster, who was part of the team that created the very first brain organoids in 2013.

The findings appeared in the journal Cell.