The brain is two separate organs that work together, rather than a single unified unit, scientists at Stanford University have discovered.
Researchers now think that at some time in human evolutionary history, the two parts of the brain may have been separated in space – similar to how jellyfish have two nervous systems in different parts of their body – before moving together.
The human brain, therefore, consists of two ancient nervous systems, which are “cleverly packaged together” and have evolved independently over millions of years, experts believe.
One primitive part, known as the hindbrain or brain stem, carries out actions vital for keeping us alive, such as keeping our hearts beating, triggering sleep and controlling breathing. It is at the back of the skull.
In contrast, the midbrain and forebrain handle high-level thinking such as language, logic and abstract reasoning.
Experts discovered that these two parts developed independently, yet could work together seamlessly.
Rayyan Jokhai, the first author, told the Telegraph: “While the front and back of the brain are built from different sources, it is remarkable that they intimately connect with one another to form a functional brain.
“A perfect example of this is the movement of muscles in our body. The front of the brain initiates the decision to make a movement while the back of the brain coordinates the fine details of this motion in space and smoothens the action.
“Additionally, movements of our face and neck are initiated by the front of the brain, but carried out directly by the back through motor neurons. This is crucial for our ability to eat, swallow and make facial expressions.”
Researchers made the discovery while trying to work out why it was impossible to grow brain cells from the hindbrain in the lab, even though it was fairly straightforward to culture the midbrain and forebrain.
The inability to grow hindbrain cells has hampered research into devastating diseases affecting the brain stem, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis, in which eating, swallowing and speech are impeded.
Neuroscientists had assumed a single progenitor cell early in development gave rise to the entire brain, but while studying the earliest moments of embryonic development in mouse embryos, they found the hindbrain followed a completely separate developmental path.
Scientists were able to peer inside the earliest moments of brain development by looking at mouse embryos at a stage known as gastrulation, when the body first starts to assemble itself into a shape, rather than being simply a sac of cells.
Human embryosare not allowed to be experimented on once gastrulation starts as it is considered unethical. But the findings are applicable to humans.
The team identified two brain progenitor cells. One, which expresses a gene called Otx2, is destined to become the forebrain and midbrain.
The other, which expresses a gene called Gbx2, is committed to forming the hindbrain. The two cell populations never overlap.
Armed with this new knowledge, they looked at the DNA packaging of the cells, and found out they were packed entirely differently. Stanford said this early developmental difference locked the cells onto different fates “like travellers on parallel tracks that never cross”.
Dr Kyle Loh, associate professor of developmental biology at Stanford, added: “We’ve shown for the first time that the front of the brain arises from a totally different progenitor cell than the back of the brain.
“Having the brain as one organ would probably be more efficient, but we rely on this primordial way to make the brain as two separate pieces.
“Our research suggests that evolution took two existing neural systems and pushed them together spatially.”
The discovery means that scientists can now grow neurons from the brain stem in a petri dish and study their functions. The researchers successfully coaxed human pluripotent stem cells, which can create any cell in the human body, to become functional hindbrain motor neurons in the laboratory.
It had been assumed that the hindbrain, controlling the vital functions of life, would have evolved first, but researchers found the same two-brain pattern in acorn worms, tiny creatures living on the ocean floor that share a distant common ancestor with humans.
It suggests that even 500 million years ago, there were separate neural systems, which now almost operate as one.
New approach to model diseases
Now that researchers can grow hindbrain neurons, it is likely to speed up treatments for SMA and amyotrophic lateral sclerosis. These diseases kill hindbrain neurons, but scientists do not know how.
“Our ability to create large numbers of human hindbrain motor neurons in a petri dish from stem cells offers a new approach to model these diseases,” added Jokhai.
“We are now studying, at high resolution, how SMA kills hindbrain motor neurons in the petri dish, and hope to use this system to discover and test SMA drugs.
“The hope would be to one day provide regenerative therapies for patients suffering from the numerous neurodegenerative diseases that exist.”
The findings were published in Nature Neuroscience.
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