Human brains grow three times larger than those of our primate cousins – and researchers have just figured out how.
In a study led by the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK, researchers identified a molecular “switch” that can make ape and human brain organoids grow like the other.
“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,” says lead researcher Madeline Lancaster.
The organoids used in the study are 3D tissues, about the size of a pea, grown in a lab from stem cells from humans, gorillas and chimpanzees. They were used to model early brain development in vitro, showing how stem cells called neural progenitors split into identical daughter cells to make neurons. The more they multiply, the more neurons will develop later.
Neural progenitors start with a cylindrical shape that makes it easy for them to multiply, but over time they elongate into a conical shape (like a stretched ice cream cone). This has previously been shown to slow their multiplication.
This new research, published in the journal Cell, used brain organoids to show that this transition occurs more slowly in humans compared to gorillas and chimpanzees – over seven days, compared to five.
The progenitor cells in human brain organoids not only retained their cylindrical shape for longer, but also split more frequently so more cells were produced. This was linked to a gene called ZEB2, which switches on sooner in gorilla brain organoids than in human. By delaying the effects of the gene, the researchers found that gorilla brain organoids develop slower and become larger.
“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,” explains Lancaster. “It’s remarkable that a relatively simple evolutionary change in cell shape could have major consequences in brain evolution.”
It is important to note, however, that organoids are only models and do not replicate how fully grown brains function – this study just provides insight into the mechanisms that take place during key stages of brain development.
Lauren Fuge is a science journalist at The Royal Institution of Australia.
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