Scientists have long treated the brain as a single organ that grows from one pool of early cells. Stanford University neuroscientist Kyle Loh and colleagues challenge this view, arguing that the human brain is two distinct nervous systems that evolved separately and were joined together over hundreds of millions of years. The discovery could also help explain why researchers have struggled for decades to grow certain types of brain cells in a lab, and open new avenues for studying devastating diseases that affect the hindbrain, or brain stem, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (also known as ALS or Lou Gehrig’s disease).
An anatomical illustration from Johannes Sobotta’s Human Anatomy, 1908.
In the study, Dr. Loh and co-authors found that the forebrain and midbrain, which govern language, reasoning and consciousness, come from a different progenitor cell than the hindbrain.
The hindbrain controls breathing, heartbeat, sleep, hunger and the muscles used in speaking and swallowing.
Working with mouse embryos, the researchers identified two cell populations that never overlap, distinguished by the genes Otx2 and Gbx2.
The cells carry different chromatin configurations, the packaging that determines which genes a cell can access.
“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 Dr. Loh, senior author of a paper published in the journal Nature Neuroscience.
“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 scientists also successfully coaxed human pluripotent stem cells to become functional hindbrain motor neurons in the lab.
These lab-grown neurons displayed all the hallmarks of authentic hindbrain cells: they exhibited waves of electrical activity called action potentials and made proteins that identify the segments of the hindbrain that control facial and swallowing muscles.
“Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” said Stanford University graduate student Rayyan Jokhai.
“This revelation explained decades of frustration in the field — scientists had been trying to turn one type of progenitor cell into another that it is fundamentally incapable of becoming.”
“In stem cell biology, people are always fixated with creating the end cell type, like the neuron.”
“But it’s important to begin at the earliest stages of embryonic development.”
“Our careful attention to that early time point allowed us to find this fundamental split in brain development.”
The findings have implications for investigating 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 authors also found the same two-origin pattern in chickens, zebrafish and acorn worms.
“Our research suggests that evolution took two existing neural systems and pushed them together spatially,” Dr. Loh said.
“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.”
“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.”
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R.T. Jokhai et al. Two parallel neural ectoderm progenitors contribute to the developing brain. Nat Neurosci, published online September 18, 2026; doi: 10.1038/s41593-026-02433-7
