In recent years, scientists have explored how hundreds of thousands of living human neurons develop – which look like the brain – and function.
These so-called brain organoids have been used to study how brains develop in layers, how they begin to form spontaneous electrical waves and may even develop. Change in zero gravity. Now researchers are using these pea-sized clusters to trace our evolutionary past.
in study Published on Thursday, a team of scientists describes how the genes likely carried by Neanderthal and our other ancient cousins produce striking changes in the anatomy and function of brain organs.
As dramatic as the changes are, scientists say it will soon be known what these changes mean for the development of the modern human brain. “This is more than a proof of concept,” said Katerina Semendeferi, co-author of the new study and an evolutionary anthropologist at the University of California San Diego.
To build on the findings, she and her co-author, Elson Muotri, have established the findings UC San Diego Archiving Center, A group of researchers focused on studying organoids along with other ancient genes and creating new ones. “Now we have a start, and we can start the search,” Dr. Semendyfi said.
Dr. Muotri started working with brain organs more than a decade ago. How to understand Zika causes birth defects, For example, he and his co-workers are organized with infected brain viruses, which prevent organoids from developing their cortex-like layers.
In other studies, researchers studied how genetic mutations help give rise to disorders such as autism. He transformed skin samples from volunteers with developmental disorders and transformed tissue into stem cells. He then developed those stem cells into brain organoids. Arranged by people with Retend syndrome, A genetic disorder resulting in some disabilities between neurons due to intellectual disability and repetitive hand movements.
Dr. Semandefy has used organoids to better understand the development of the human mind. In previous work, she and her co-workers have found that in apes, neurons that develop in the cerebral cortex remain close to each other, whereas in humans, cells can crawl long distances. “It’s a completely different organization,” she said.
But this comparison spreads across a huge gap in evolutionary times. Our ancestors separated from chimpanzees about seven million years ago. For millions of years after that, our forefathers were bipedal apes, gradually achieving great heights and brains, Neanderthals, Denisovans and other hominins.
It is difficult to track the evolutionary changes of the brain along the way. Our own dynasty separated from Neanderthals and Denisovans about 600,000 years ago. After that split, fossils show up, our brain eventually became more rounded. But what it means for 80 billion neurons is difficult to know.
Dr. Muotri and Drs. Semendefi studied together with evolutionary biologists, who study fossil DNA. Those researchers have been able to recreate the entire genome of Neanderthals by pececing together genetic fragments from their bones. Other fossils have found the genomes of Denisovans, which diverged from Neanderthals 400,000 years ago and survived for thousands of generations in Asia.
Evolutionary biologists identify 61 genes that may have played an important role in the development of modern humans. Each of those genes has a mutation that is unique to our species, which has been generated for some time over the last 600,000 years, and has a major impact on the proteins encoded by these genes.
Dr. Muotri and his colleagues wondered what would happen to a gene organoid if they removed one of those mutations, which replaces a gene back in the genome of our ancestors. The difference between an ancestral organism and a commoner may provide clues as to how mutation affected our development.
It took many years for scientists to land this experiment. They struggled to find a way to properly convert genes into stem cells before coaxing them to convert into organoids.
Once they understood a successful approach, they had to choose a gene. Scientists worried that they might choose a gene for their first experiment that would do nothing for organoids. He said how to increase your chances of success.
“Our analysis told us, ‘Let’s find a gene that replaces a lot of other genes,” Dr. Muotri said.
One gene on the list seemed particularly promising in that regard: NOVA1, which forms a protein that then guides the production of proteins from many other genes. The fact that it is mainly active only in the developing brain has made it more attractive. And the human mutation in NOVA1 is not found in other vertebrates, living or extinct.
Dr. Muotri’s associate, Kleber Trujillo, grew a batch of organoids carrying the ancestral variant of the NOVA1 gene. After placing it under a microscope next to a simple brain organ, he gave Dr. Invited to see Muotri.
The ancestral NOVA1 organoid had a different rounded texture, with a rugged popcorn texture instead of a smooth circular surface. “At that point, things started,” Dr. Muotri recalled. “I said, ‘Okay, this is doing something.” “
The proportion of different types of brain cells in the ancestral organisms was also different. And neurons in the paternal organoids started firing spikes of electrical activity a few weeks earlier than in modern humans. But electrical spikes also took longer to settle into waves.
Other experts were surprised that a single genetic mutation could have such obvious effects on organoids. He expected microscopic shifts that can be difficult to observe.
“It seems that the authors found the needle in Hast based on a very beautiful study design,” said Philip Gunz, a paleontologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “
Simon Fisher, director of the Max Planck Institute for Psychologists in the Netherlands, said the results came from a mixture of hard work and some good luck. “There will be some degree of certainty,” he said.
Although researchers do not know what changes in organoids mean for our evolutionary history, Drs. Muotri suspects that there may be connections with thinking made possible by different types of minds. “The correct answer is, I don’t know,” he said. “But everything we see in neurodevelopment at a very early stage may have an implication later in life.”
In the new research center, Drs. Semendefi plans to conduct careful physical studies on brain organs and compare them to the brains of human embryos. This comparison will help in understanding the changes observed in the ancestral NOVA1 organoids.
And Dr. Muotri’s team is working through a list of 60 other genes, so that Drs. More organoids can be produced to investigate Semandeferi. It is possible that the researchers were not so lucky as they were in their first attempt and would not see much difference with some genes.
“But others may be similar to NOVA1 and point to something new – some new biology that allows us to reconstruct an evolutionary path that helped us become who we are”.