Researchers have inserted a human gene into the brains of monkeys to make them larger and more curly in disturbing laboratory experiments.
Experts found that the insertion of the gene, called ARHGAP11B, resulted in a larger neocortex in the fetus of a common marmoset.
The neocortex is the deeply grooved outer layer of the brain involved in reasoning, language, conscious thinking, and other important functions.
ARHGAP11B, found in humans but not non-human primates or other mammals, triggered the monkeys’ brain stem cells to form more stem cells and enlarged the brain.
Genetically modified marmoset brains were found to mimic the natural bumps and depressions in human brains, known as gyri and sulci, respectively ̵
The experiments are evocative of the more recent Planet of the Apes movies, in which genetically modified primates wage war on humanity.
Image a brain half of a marmoset fetus grown with human gene ARHGAP11B. Cell nuclei seen in white. Researchers say that the bumps in the brain mimic those of a human brain. The left arrow indicates a sulcus (a depression or groove in the cerebral cortex), while the right arrow indicates a gyrus (a ridge-like height).
Researchers developed a total of seven marmoset fetuses, all in the womb (inside the womb) and were obtained on day 102 of pregnancy by a cesarean section for analysis.
‘We actually found that the neocortex of the common marmoset brain was enlarged and the brain surface was folded,’ said study author Michael Heide at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG).
”[We also saw] increased number of neurons in the upper layer, the type of neuron that increases in primate development. ‘
The human neocortex is about three times larger than that of our closest relatives, chimpanzees.
Andy Serkis plays Caeser in Rise Of The Planet Of The Apes (2011), a chimpanzee whose intelligence increases from being exposed in the womb to a drug called ALZ-112
During evolution, our brains folded into the markedly wrinkled appearance to fit into the confined space of our skull, while at the same time the surface area of the neocortex could be greatly increased.
Images of the 101-day-old genetically engineered marmoset fetus, approximately 50 days away from its normal date of birth, show this induced folding in the team’s experiments.
This is in contrast to marmoset brains, which are much smoother than human brains as well as smaller ones.
Normal and ARHGAP11B fetal marmoset brain. Yellow lines indicate the boundaries of the cerebral cortex; white lines that develop the cerebellum; arrowheads, folds. Scale rods: 1 mm
The walnut-like appearance of the human brain, an evolutionary trait to increase its surface area for neurons (nerve cells), is made of what is called sulcus (depression) and gyrus (height)
ARHGAP11B may have caused neocortex expansion during human development, according to the team, which also included experts from the Central Institute for Experimental Animals (CIEA) in Kawasaki and Keio University in Tokyo, Japan.
Japanese scientists, including Hideyuki Okano, had pioneered the development of a technology for generating transgenic non-human primates.
Okano’s laboratory at the RIKEN Center for Brain Science in Wako, Japan was the first in the world to produce transgenic Muslims with germline transmission (GT).
GT is a technique in which embryonic stem cells contribute to reproductive cells in a mammal (germ cells) and are genetically transmitted to its offspring.
However, there was no use of GT for this project for the simple reason that the transgenic marmoset fetuses were not allowed to be born.
Pictured in this illustration, a side view of the brain on the common marmoset that lacks the walnut-like grooves in a human brain
‘We limited our analyzes to marmoset fetuses because we expected that the expression of this human-specific gene would affect neocortex development in the marmoset,’ said study author Wieland Huttner at MPI-CBG.
‘Given the potential unpredictable consequences for postnatal brain function, we considered it a prerequisite – and mandatory from an ethical point of view – to first determine the effects of ARHGAP11B on the development of fetal marmoset neocortex.’
ARHGAP11B originated through a partial replication of the ubiquitous gene ARHGAP11A about five million years ago along the evolutionary lineage that led to Neanderthals, Denisovans, and modern humans.
The new study, published in the journal Science, follows the work of MPI-CBG in 2015 to identify ARHGAP11B.
Researchers isolated different subpopulations of human brain stem cells and identified which genes are active in which cell type.
Tests at the time on mouse embryos revealed that the gene can have a huge impact on brain development.
Researchers found a single gene that may be responsible for the large number of neurons found uniquely in the human brain in 2015. When this gene was inserted into the brain of a mouse embryo (pictured), it caused the formation of many more neurons (colored red)
ARHGAP11B, when expressed in mice at non-physiologically high levels, caused an enlarged neocortex.
Embryos injected with the gene grew larger brain areas, and some developed the wrinkled surface characteristic of the human brain.
‘It’s so cool that a small gene alone can be sufficient to influence the stem cell phenotype, which contributed most to the expansion of the neocortex,’ said lead author Marta Florio at MPI-CBG WordsSideKick.com.
However, the gene’s relevance to primate development had been unclear until now, researchers said.
HOW OUR BRAIN HAS GROWN
About 3.8 million years ago, our ancestors Australopithecus afarensis had a brain that was 30 cubic centimeters (500 cubic centimeters) in volume.
About 1.8 million years ago, Homo erectus had a brain twice the size of Australopithecus afarensis.
When the Neanderthals and Denisovans arrived, the brain had grown to 1.4 liters (volume).
Despite this increase in size, researchers believe that human intelligence may have more to do with how brain cells form, how big the brain grows.
The human-specific gene ARHGAP11B originated through a partial duplication of the ubiquitous gene ARHGAP11A about 5 million years ago along the genus that led to Neanderthals, Denisovans, and modern humans, after this genus was separated from the one that led to the chimpanzee.
A sequence of 47 amino acids is essential for ARHGAP11B’s ability to increase brain stem cells.