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Scientists have inserted a human gene into the brains of monkeys to make them bigger and more wrinkled in baffling lab experiments.
Experts found that 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 that is involved in reasoning, language, conscious thought, and other important functions.
ARHGAP11B, found in humans but not in non-human primates or other mammals, triggered the formation of additional brain stem cells from monkey brain stem cells, which enlarged the brain .
Genetically engineered marmoset brains have been found to mimic the natural bumps and indentations in the human brain, known as gyri and sulci, respectively – an evolutionary trait in humans to increase the area of neurons (nerve cells) .
The experiences are reminiscent of recent Planet of the Apes films, where genetically modified primates wage a war against humanity.
Imagine a cerebral hemisphere of a marmoset fetus cultivated with the human ARHGAP11B gene. Cell nuclei seen in white. Scientists say that the bumps in the brain mimic those in a human brain. The left arrow indicates a sulcus (a depression or groove in the cerebral cortex), while the right arrows indicate a gyrus (a ridge-like elevation).
The researchers developed a total of seven marmoset fetuses, all in utero (inside the uterus) and were obtained on day 102 of the pregnancy by cesarean section for analysis.
“We did indeed find that the neocortex of the common marmoset’s brain was enlarged and the surface of the brain was folded back,” said study author Michael Heide at the Max Planck Institute for Molecular Cell Biology and Genetics ( MPI-CBG).
‘[We also saw] increase in the number of upper layer neurons, the type of neuron that increases in the evolution of primates.
The human neocortex is about three times the size of our closest relatives, chimpanzees.
Andy Serkis stars as Caeser in Rise Of The Planet Of The Apes (2011), a chimpanzee whose intelligence is increased after being exposed in the womb to a drug called ALZ-112
During evolution, our brains have folded into the distinctive wrinkled appearance to fit within the tight space of our skull while allowing the area of the neocortex to be greatly increased.
Images of the 101-day-old genetically modified marmoset fetus, about 50 days from its normal birth date, show this induced folding in the team’s experiments.
This contrasts with the normal marmoset brains, which are much smoother than human brains, as well as smaller.
Normal fetal marmoset brains and ARHGAP11B. Yellow lines indicate the boundaries of the cerebral cortex; white lines, development of the cerebellum; arrowheads, folds. Scale bars: 1 mm
The nut-like appearance of the human brain, an evolutionary trait to increase its surface area for neurons (nerve cells), is made up of what is called the sulcus (depression) and gyrus (elevation)
ARHGAP11B may have caused the neocortex to expand during human evolution, according to the team, which also included experts from the Central Institute for Experimental Animals (CIEA) in Kawasaki and Keio University in Tokyo, in Japan.
Japanese researchers, including Hideyuki Okano, had pioneered the development of technology to generate transgenic non-human primates.
Okano’s lab at the RIKEN Center for Brain Science in Wako, Japan, was the first in the world to produce germline-transmitted (GT) transgenic marmosets.
GT is a technique in which embryonic stem cells contribute to a mammal’s reproductive cells (germ cells) and are transmitted genetically to its offspring.
However, GT was not used for this project, for the simple reason that transgenic marmoset fetuses were not allowed to be born.
Pictured in this illustration, a lateral view of the common marmoset’s brain, which lacks the nut-shaped grooves of a human brain
“We limited our analyzes to marmoset fetuses because we predicted that expression of this specific gene in humans would affect the development of the neocortex in the marmoset,” said study author Wieland Huttner of MPI- CBG.
“ In light of the potential unpredictable consequences for postnatal brain function, we considered it a prerequisite – and ethically mandatory – to first determine the effects of ARHGAP11B on the development of the brain. neocortex of the fetal marmoset. ”
ARHGAP11B was born from a partial duplication of the ubiquitous ARHGAP11A gene approximately five million years ago along the evolutionary lineage leading to Neanderthals, Denisovans, and modern humans.
The new study, which was published in the journal Science, follows work at MPI-CBG in 2015 to identify ARHGAP11B.
The researchers isolated different subpopulations of human brain stem cells and identified which genes are active in which type of cell.
Tests carried out at the time on mouse embryos revealed that the gene can have a huge impact on brain development.
Scientists discovered a single gene that could be responsible for the large number of neurons found only 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 (stained red)
ARHGAP11B, when expressed in mice at non-physiologically elevated levels, caused an enlarged neocortex.
Embryos injected with the gene developed larger brain regions and some developed the characteristic wrinkled surface of the human brain.
“ It’s so cool that a small gene alone might be enough to affect the phenotype of the stem cells, which contributed the most to the expansion of the neocortex, ” said lead study author Marta Florio of MPI-CBG at LiveScience.
However, the relevance of the gene to the evolution of primates was not clear until now, according to the researchers.
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