Mini-Neanderthal brain to grow in petri dishes

The pea-size, Neanderthalized mini brain that the ancestral NOVA1 gen. Each “pea” has about 400,000 cells. Credit: Alysson Muotri

Neanderthals went extinct about 40,000 years ago, but thanks to the advanced science, there is now a lab in California that has petri dishes filled with pea-size versions of the cavemen, the brain.

Why are researchers to grow and study these mini brains? The reason, they say, is that this small neural nodule may reveal why Neanderthals died out and Homo sapiens went on to conquer much of the planet.

“The neanderthals are fascinating because they shared the Earth with us, and there is now genetic evidence that we actually bred with them,” study leader Alysson Muotri, director of the University of California, San Diego (UCSD) Stem cell Program, told Science. [11 s of the Body Grown in the Lab]

Perhaps the genetic differences between the Neanderthal and the human brain to explain their demise and our success, Muotri said. In other words, it is possible that the man achieved great technological progress, because we have advanced neural networks, while Neanderthals didn’t.

Muotri presented of the research that still needs to be published in a peer-reviewed journal, a UCSD conference called Imagination and the Origins of Man on 1 June.

The building of a brain

In order to investigate, Muotri and his colleagues compared the genomes of Neanderthals (previously extracted from fossil bones and by other researchers) with that of the modern man. Out of 200 candidate genes, which showed that there are significant differences between the two species, the researchers decided to focus on just one: a master gene expression regulator known as NOVA1.

NOVA1 is highly expressed during neurodevelopment and is associated with neural disorders, such as autism and schizophrenia, Muotri said. The NOVA1 gene is remarkably similar in humans and the Neanderthals — just a single base pair (or a few of the DNA letters) is different between the two.

Scientists have grown mini human organs, known as organoids in the lab. To grow mini-Neanderthal brain (which the researchers playfully called Neanderoids), they used the gene-editing tool known as CRISPR “Neanderthalize” human pluripotent stem cells, or immature cells that can develop into any cell in the body, Muotri said.

Then, with the help of their in-house protocol, “we persuaded the stem cells in a brain organoid,” a process that takes between six and eight months, Muotri said. Now grown, the Neanderoids measure approximately 0.2 inches (0.5 centimeters) wide, “as you can see with the naked eye once they’re adults,” he said.

The mini-brains can not grow larger, because they are not vascularized, meaning that they do not have a blood supply. On the contrary, the mini brain cell (there are up to 400,000 per brain) receive nutrients by diffusion.

“It is possible that in the future we can grow a larger organoid,” Muotri said. “We are working on this by creating bio-printed artificial blood vessels in them.”

Large differences

The man in the lab-grown brain are usually around, but the Neanderoids not. Instead, the Neanderthals mini brain had elongated tubular structures that gave them a popcorn-like shape,” Muotri said.

Some of the Neanderoid cells also migrated faster from the source during the development, which could explain the unusual popcorn formation, he noted. [3D Images: Exploring the Human Brain]

In addition, Muotri added that the Neanderoids not as many synaptic connections, or connections between neurons, and had altered neuronal networks. These characteristics resemble those of the human mini brains grown from people with autism, he said. However, it is difficult to say what this parable means, if anything, he said.

“A correlation does not mean that they are the same,” Muotri said. “We can only speculate about this at this stage.”

However, the research is still in its early stages, and it is important to note that the project has a few limitations, said Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, who was not involved in the research.

“Organoids are far from able to tell us how adult brain,” said Pääbo journal Science. He and his colleagues are also engaged in the making of mini-Neanderthal brain, and the method can sometimes introduce unintended mutations, said Pääbo.

Even so, with controlled experiments, “I am very hopeful we will overcome that doubt,” said Pääbo Science Magazine, adding that he hopes to compare Neanderoids with mini brain of the chimpanzee or the human cells.

What is the next

Muotri’s team is now the approach of other sci-fi-like challenge. They have figured out a way for robots to measure electrical brain signals that are sent by the human mini-brain. By connecting the robots with the mini brain, they hope to create a ‘learning feedback loop’, which is the brain direct the robot to explore the environment.

“Ultimately we want to compare the Neanderthalized organoid [with the robot] to test his ability to learn,” Muotri said.

In all, the organoid research can reveal which genetic variants are crucial for human success. “By doing this systematically, we will learn what are the genetic changes that make us uniquely human and why they were positively selected,” Muotri said.

Original article on Live Science.



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