Lab-grown ‘organoids’ reveal why humans have such big brains © Getty Images

Lab-grown ‘organoids’ reveal why humans have such big brains

Humans' brains contain up to three times as many neurons as those of gorillas or chimpanzees.

One of the key traits that sets humans apart from other apes, such as gorillas and chimpanzees, is the size of our brains. Human brains are much larger and contain up to three times as many neurons.

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Uncovering the exact mechanism behind this difference in brain development has long proven difficult for scientists.

Now, a team at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK, may have found the answer using brain ‘organoids’ grown from stem cells taken from human, gorilla and chimpanzee stem cells.

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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. But as they mature and slow their multiplication, they elongate, forming a shape like a stretched ice-cream cone.

Previous research in mice found that this process occurs within hours. In their new study, the researchers found that this process takes around five days in gorillas and chimpanzees but around seven in humans. This extra time allows them to produce more neurons, the team say.

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

Human brain organoids grow substantially bigger than gorilla and chimpanzee (left to right). These brain organoids are 5 weeks old. © S.Benito-Kwiecinski/MRC LMB/Cell
Human brain organoids grow substantially bigger than gorilla and chimpanzee (left to right). These brain organoids are 5 weeks old. © S.Benito-Kwiecinski/MRC LMB/Cell

“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 learnt something fundamental about the questions I’ve been interested in for as long as I can remember – what makes us human.”

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.

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They found differences in a gene called ‘ZEB2’, which was turned on sooner in gorilla brain organoids than in the human organoids. Turning this gene on sooner in the human brain organoids led to them developing in a more gorilla-like way, while turning it on later led the gorilla organoids to develop in a more human-like way.

Reader Q&A: Is it possible for humans and chimpanzees to interbreed?

Asked by: Pauline Hetherington, Surrey

Genetic analysis suggests there may have been a long period of cross-breeding between early ancestors of the humans and chimpanzees, before they finally split into the Homo and Pan (chimp) genera around six million years ago. But today, although humans and chimpanzees share 99 per cent of the DNA sequences that code for proteins, that DNA is packaged differently into the chromosomes.

The human chromosome number two is actually two ape chromosomes joined end-to-end, and nine other chromosomes have inverted sequences of genes compared with their equivalents in chimps. Humans and chimps also have differences in their individual genes that are far bigger than the differences between any two unrelated humans.

These are big obstacles, but not necessarily insurmountable. Other animals with comparable genetic differences, such as zebras and horses, have bred successfully in the past, although the offspring are almost always sterile. There are documented cases of Soviet experiments in the 1920s where artificial insemination was attempted using female chimps and human sperm. However, none of these experiments resulted in a pregnancy, much less the birth of a ‘humanzee’. There are various urban legends of other later experiments in different labs worldwide, but there’s no evidence that the result was ever any different.

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