Every time you swallow, a complicated chain of muscles and nerves springs into action. Your breathing briefly pauses, muscles in your throat contract, and everything moves in the right direction without you consciously controlling any of it.
Now, Stanford researchers have found evidence that the brain regions controlling those automatic functions may have a surprisingly different origin from the parts responsible for conscious thought.
The Brain May Have Two Very Different Beginnings
Researchers at Stanford Medicine examined an extremely early stage of development and found two distinct populations of progenitor cells. One population was associated with the forebrain and midbrain, while the other was committed to producing the hindbrain.
The two groups remained separate and did not switch developmental paths. The finding suggests that the front and back of the brain may have distinct cellular origins much earlier in development than previously understood.
“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,” Stanford Medicine developmental biologist Kyle Loh said. The findings were published in Nature Neuroscience on September 18, 2026.
The research focused on developing mouse embryos, where the scientists identified one group of cells switching on Otx2 and another switching on Gbx2. The Otx2 cells were committed to the forebrain and midbrain, while the Gbx2 cells were committed to the hindbrain.
The Separation Starts Earlier Than Expected
The distinction was not limited to the genes being activated. The researchers also found differences in chromatin, the material that packages DNA and helps determine which parts of the genetic code a cell can access.
The paper described the progenitor cells as having “diverging chromatin landscapes foreshadowing future forebrain/midbrain vs. hindbrain identities.” In other words, the cells were already being pushed toward very different futures at an extremely early stage.
Rayyan Jokhai, a graduate student and co-first author, said the result challenged an assumption he had made about the organ he was studying. “I was surprised at our findings because the word ‘brain’ implies a contiguous organ that likely has a singular origin,” Jokhai said.
The researchers found that the hindbrain lineage did not simply branch from a common developmental population. Instead, it followed its own developmental path from the early progenitor cells they examined.
Two Cell Populations, Two Destinations
The findings can be broadly divided into two developmental paths:
- Otx2 progenitors: These cells were associated with the developing forebrain and midbrain, regions involved in higher-order functions and conscious activity.
- Gbx2 progenitors: These cells were associated with the developing hindbrain, which controls numerous automatic functions, including breathing and swallowing.
- Separate lineages: The researchers found that the two populations did not mix or convert into one another during the developmental stages studied.
That distinction could change how researchers approach one particularly difficult problem in stem cell biology: creating human hindbrain neurons in the laboratory.
Scientists Had Been Starting With the Wrong Cells
Researchers have spent years trying to generate human hindbrain neurons from stem cells because these cells are involved in some of the body’s most basic functions. The neurons controlling swallowing and breathing can also be affected by devastating neurological diseases, yet they cannot simply be removed from a living person’s brainstem for laboratory study.
Stem cells offer scientists a potential alternative. If researchers can reliably guide them into becoming specific human neurons, they can create laboratory models for studying disease and testing possible treatments.
Previous efforts struggled to produce the precise hindbrain cells scientists wanted. The Stanford findings offer an explanation for why those attempts may have repeatedly failed.
“Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” Jokhai said. He also pointed to a broader issue in stem cell research, saying, “In stem cell biology, people are always fixated with creating the end cell type, like the neuron.”
The new research suggests that scientists need to pay much closer attention to the identity of the starting cell.
Stanford Grew Hard-to-Make Neurons in a Dish
After identifying the appropriate developmental starting point, the researchers guided human pluripotent stem cells into hindbrain motor neurons associated with rhombomeres 5 and 6. These are developing hindbrain segments involved in supplying muscles associated with facial movement and swallowing.
The resulting laboratory-grown neurons showed characteristics expected from those cells. They produced action potentials, the electrical signals neurons use to communicate, and produced proteins associated with the relevant hindbrain segments.
The paper describes these cells as previously difficult to generate in vitro. Being able to create them in a laboratory gives researchers a new way to study human hindbrain neurons without needing access to living brain tissue.
“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,” Loh said.
That could be particularly useful for researchers studying diseases that damage these neurons.
The Discovery Could Help Researchers Study ALS
The potential medical value of the work centers partly on spinal muscular atrophy and amyotrophic lateral sclerosis, or ALS. Both conditions can involve the degeneration of motor neurons that control essential movements, including swallowing and breathing.
Researchers can now potentially use laboratory-grown hindbrain motor neurons to investigate how these cells develop and function. They can also examine what happens to the cells when disease processes are introduced in controlled laboratory settings.
Jokhai said the researchers now have “a model to better understand these devastating diseases, and work toward regenerative therapies for them.” The study does not demonstrate a new treatment for ALS or spinal muscular atrophy, but it provides a model that could support future research.
The hindbrain also regulates other automatic processes, including hunger. That gives the research another connection to the neural circuits targeted by weight-loss medications such as semaglutide.
The Pattern Appeared Across Other Animals
The researchers then looked beyond mammals to see whether the developmental pattern might be more widespread. They found evidence of the same broad two-origin pattern in chickens, zebrafish and acorn worms.
Acorn worms are small marine animals that burrow into the seafloor and share a distant common ancestor with humans. Their lineage diverged from ours roughly 550 million years ago, according to the supplied research account.
The team also considered jellyfish, which split from the lineage leading to humans even earlier. Jellyfish have nervous systems arranged very differently from ours, including neural structures at opposite ends of their bodies.
“Our research suggests that evolution took two existing neural systems and pushed them together spatially,” Loh said. The paper describes the brain as potentially being “a composite organ emanating from two lineage restricted progenitors.”
That evolutionary explanation remains a hypothesis. The researchers did not directly observe ancient organisms combining two separate nervous systems.
The “Two Brains” Interpretation Has a Major Caveat
The most dramatic version of this story can easily be misunderstood. The study does not show that humans have two separate brains functioning independently inside the skull.
The brain remains one functioning organ, and the researchers are describing its developmental origins rather than claiming that the adult brain consists of two independent organs.
The lineage experiments were performed using mouse embryos, while the human experiments involved pluripotent stem cells grown in a laboratory. No human embryos were studied.
The evolutionary explanation is also an inference based on developmental patterns observed in living organisms. The authors use the word “postulate” when discussing the idea that the brain could represent a composite organ with two lineage-restricted origins.
That makes the most solid result somewhat less sensational, but potentially more useful: scientists have identified a developmental route that allows them to grow specific human hindbrain motor neurons that were previously difficult to produce.
The Swallow Reveals What Makes This So Strange
Every swallow depends on neural machinery operating below conscious awareness. The same is true for the breathing patterns that continue while a person sleeps, along with countless other automatic processes controlled by the hindbrain.
Stanford’s research suggests that the cells behind some of those functions followed a separate developmental path from the cells that eventually formed the brain’s front regions. That separation appears surprisingly early in development and may have roots shared across a much older stretch of evolution.
For most people, that is a bizarre piece of biology. For researchers studying ALS and other neurological diseases, the more important development is practical: they now have a way to grow specific human hindbrain motor neurons and study what happens when those cells malfunction.
The brain may look like one continuous organ, but its earliest construction appears to have been far more divided than the textbook diagrams suggest.
