Monkeys with humanized brains
Biologists have grown a monkey embryo with a more "human" cerebral cortex
Maria Azarova, Naked Science
The increase in the human brain occurred during evolution and was associated with our cognitive abilities, such as thinking and speech development. The ARHGAP11B gene, which is found only in humans, is known for its role in the expansion of the neocortex – the "new cortex" of the brain, which consists of numerous folds and furrows divided into the right and left hemispheres, and is responsible for more developed neural functions – speech, sensory perception, execution of motor commands and conscious thinking.
We got ARHGAP11B about five million years ago – shortly after there was an "evolutionary split" between chimpanzees and the ancestors of modern humans. This gene arose as a result of a mutation when another gene – ARHGAP11A – was copied or duplicated. However, the version of ARHGAP11B, known as "hereditary version B", is not what people have today. Scientists believe that another mutation subsequently occurred, which created a human-specific gene. It was used in their experiments by scientists from the Max Planck Institute of Molecular Cell Biology, which is described in the journal Science (Heide et al., Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset).
"This specific sequence is extremely necessary for the gene's ability to strengthen the corresponding brain stem cells during development," says Wieland Hattner, one of the authors of the article. Biologists have grown embryos of marmosets with the ARHGAP11B gene initially embedded. This was done with the help of a lentivirus, which has the ability to deliver a significant amount of genetic material to the host cell and replicate in non-dividing cells.
In the case under consideration, the lentivirus just contained ARHGAP11B, as well as a protein marker that allowed scientists to see exactly where this gene is expressed. So, on the 101st day of embryo development (50 days before the birth of the animal), the neocortex of primates became larger, thicker, had more folds and furrows compared to the cerebral cortex of ordinary, non-transgenic monkeys.
The brain of an ordinary wild monkey and its transgenic congener with an enlarged neocortex / © Heide et al. / MPI-CBG.
Previous studies have already demonstrated similar results in transgenic mice and ferrets. However, using these animal models did not mean that the embedded gene would be expressed in them in the same way as in humans. Therefore, the authors of the new work decided to conduct an experiment on an organism that would be closely related to a person.
"We thought the monkey would be the best model because the macaque's neocortex has many features that it shares with our large and complex neocortex. <…> We limited ourselves to experiments on embryos, since we would not be able to predict the consequences of the inclusion of this gene and their impact on the postnatal development of monkeys, and this is critically important from an ethical point of view. As we expected, its activation noticeably changed the development of the cortex of the igrunok brain," adds Hutner.
The study also demonstrated that the added gene, in addition to increasing the size and number of folds in the neocortex, controls the production of certain neurons that develop later and are important for processing higher-order information.
"There is a whole list of genes that, in our opinion, can play a role in what makes us unique. However, it was extremely rare that we could prove that they were the participants in this process. The new study really brings ARHGAP11B to the top of the list. This is a gene that may well be important for the development of the human brain," the authors note.
In addition, studying the role of ARHGAP11B may be important for understanding diseases such as schizophrenia, mental retardation or epilepsy. And a brain that develops too large (macrocephaly) causes a number of neurological and behavioral disorders, including autism. A more detailed understanding of unique human genes, such as ARHGAP11B, will help in the development of new therapies. Biologists also suggest that this gene may be useful for growing stem cells.
However, the idea of using ARHGAP11B or others like it in experiments to change the structure and functions of the human brain raises many ethical questions. "You have to be very careful,– Hutner stresses. – If you carry out genetic manipulations on people, then you can do it only if you want to cure a disease based on a pathological mutation. <...> But it is impossible to try to "improve" people."
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