Next time you have a good, hard think, just know you’re racking your brains.
Yes, you read that right — it’s plural.
Scientists at Stanford University have discovered that the human brain isn’t one, but two organs. And the revelation could be huge for researching treatment for serious diseases including ALS.
The study, published today in the journal “Nature,” showed that the brain is essentially made up of two distinct nervous systems that develop separately.
First, there’s a more primitive part called the hindbrain. There’s also the forebrain and midbrain, which handle higher-level thinking and make us distinctly human, from writing poetry and doing math to wondering about our own origins.
This discovery helped the researchers to grow a crucial type of brain cell in the lab for the first time.
The breakthrough could help close a gap that has hampered research into spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease or ALS) and other devastating diseases affecting the brain stem, potentially opening new avenues for understanding what goes wrong in these conditions.
“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,” said Kyle Loh, senior author and associate professor of developmental biology.
“Our discovery means that we can now grow neurons from the back of the brain, the hindbrain, in a Petri dish and study their functions.”
The brain’s two developmental paths
The adult brain is composed of three main regions.
The forebrain controls higher-level thinking like language, consciousness and abstract reasoning, while the midbrain manages functions including vision and hearing, movement control, arousal and pain.
At the back of the skull, the hindbrain — often called the brain stem — handles vital, life-sustaining functions, including regulating breathing, heartbeat, swallowing and digestion, and basic movement coordination.
In both SMA and ALS, specific hindbrain neurons progressively stop functioning, causing patients to lose their ability to swallow and, eventually, breathe.
For decades, scientists have struggled to grow hindbrain neurons in the lab because the prevailing theory was that all parts of the brain developed from the same source.
Scientists examined the earliest stages of embryonic development in mice and found that the hindbrain actually follows a separate developmental path. It develops alongside the forebrain and midbrain, rather than branching off from it.
They identified two types of brain progenitor cells: one expressing a gene called Otx2 that develops into the forebrain and midbrain, and another expressing Gbx2 that develops into the hindbrain. The two types of cells never overlap, even in the earliest stages of development.
“Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” graduate student Rayyan Jokhai said.
The finding suggests that decades of frustration in this area of research stemmed from scientists attempting to turn one type of progenitor cell into another that it is intrinsically unable to become.
A new way to study deadly brain diseases
Based on their findings, the researchers were able — for the first time — to successfully grow functional hindbrain motor neurons in the lab.
The lab-grown neurons had the key characteristics of real hindbrain cells, creating new opportunities to study potential treatments for SMA, ALS and other conditions affecting the brain stem.
“Now we have a model to better understand these devastating diseases and work toward regenerative therapies for them,” Jokhai said. “This is a very exciting new frontier in brain research.”
The researchers traced this two-origin brain pattern back more than 550 million years of evolutionary time and found the same arrangement in chickens and zebrafish, along with acorn worms and jellyfish, both distant common ancestors of humans.
“I was surprised at our findings because the word ‘brain’ implies a contiguous organ that likely has a singular origin,” Jokhai said.
“But even 500 million years ago, there were these separate neural systems, which now almost operate as one, which is very cool.”
