Brain organoids shed light on the evolution of the human brain.
Great ape animal studies have long been prohibited in Europe due to ethical concerns. An alternative to using animals in studies is the use of so-called organoids, which are three-dimensional cell structures that can be generated in the lab and are just a few millimeters in size.
These organoids can be created using pluripotent stem cells, which then subsequently develop into particular cell types like nerve cells. The study team was able to create both chimpanzee and human brain organoids by using this method.
“These brain organoids allowed us to investigate a central question concerning ARHGAP11B,” says Wieland Huttner of the Max Planck Institute of Molecular Cell Biology and Genetics, one of the three lead authors of the study.
“In a previous study, we were able to show that ARHGAP11B can enlarge a primate brain. However, it was previously unclear whether ARHGAP11B had a major or minor role in the evolutionary enlargement of the human neocortex,” says Wieland Huttner.
To clarify this, the ARGHAP11B gene was first inserted into chimp organoid brain ventricle-like structures. Would the ARGHAP11B gene cause the chimpanzee brain’s brain stem cells to proliferate, which is required for the neocortex to increase in size?
“Our study shows that the gene in chimpanzee organoids causes an increase in relevant brain stem cells and an increase in those neurons that play a crucial role in the extraordinary mental abilities of humans,” said Michael Heide, the study’s lead author, who is head of the Junior Research Group Brain Development and Evolution at the German Primate Center and employee at the MPI-CBG.
When the ARGHAP11B gene was knocked out in human brain organoids or the ARHGAP11B protein’s function was inhibited, the number of these brain stem cells was reduced to that of a chimpanzee.
“We were thus able to show that ARHGAP11B plays a crucial role in neocortex development during human evolution,” says Michael Heide. Julia Ladewig of HITBR, the third of the lead authors, adds: “Given this important role of ARHGAP11B, it is furthermore conceivable that certain maldevelopments of the neocortex may be caused by mutations in this gene.”
Reference: “Human-specific ARHGAP11B ensures human-like basal progenitor levels in hominid cerebral organoids” by Jan Fischer, Eduardo Fernández Ortuño, Fabio Marsoner, Annasara Artioli, Jula Peters, Takashi Namba, Christina Eugster Oegema, Wieland B. Huttner, Julia Ladewig and Michael Heide, 13 September 2022, EMBO Reports.