At five weeks old, human brain organoids (left) are far bigger than those from a gorilla (top right) and a chimpanzee (bottom right)
Miniature brains of humans, gorillas and chimpanzees developed in the lab have shown how our brains grow much larger than those of other apes.
At birth, our brains have around three times as many neurons as those of newborn chimpanzees and gorillas, despite having similar gestation periods. To understand why, Madeline Lancaster and her colleagues at the MRC Laboratory of Molecular Biology in Cambridge, UK, grew miniature brain organoids to mimic early brain development in humans, gorillas and chimpanzees.
First, they collected adult cells from the three species and genetically reprogrammed them to resemble cells found in an early embryo – these are called induced pluripotent stem (iPS) cells. “You sort of trick them into thinking they’re embryonic again,” says Lancaster.
The team then grew brain organoids using these iPS cells. Similar to actual brains, the human miniature brains grew larger than the organoids of gorillas and chimpanzees as early as two days in. By five weeks, the human brain organoids were around twice as large as the other ape brain organoids, measuring around four millimetres across, says Lancaster.
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“This early stage of development is usually very inaccessible,” says Lancaster. “It’s a kind of black box in human biology.” We know very little about it in gorillas and chimpanzees too. “Apes are an endangered species, so ethically, we wouldn’t want to do experiments at this stage. We usually don’t even know the gorilla is pregnant this early on.”
The researchers then analysed genes in the brain organoids and found differences in the expression of a gene called ZEB2, with the gorilla and chimpanzee brain organoids turning it on earlier than the human organoids.
The ZEB2 gene controls cell shape and motility. “Essentially, when this gene is switched on, the cells are less ‘sticky’ and can leave and go elsewhere,” says Lancaster. By delaying the gene’s activation, early human brain cells are able to stick together and multiply for longer before specialising into mature nerve cells, she says.
To make sure ZEB2 was responsible, the team switched the gene on earlier in the human organoids and later in the gorilla organoids. “The [human] brain organoids started to look like the ape cells and, vice versa, the gorilla cells actually ended up looking like the human cells,” says Lancaster.
Journal reference: Cell, DOI: 10.1016/j.cell.2021.02.050