The human brain may not be a single, unified organ after all. According to a study published in Nature Neuroscience, the front and back regions of the brain develop from two entirely different types of progenitor cells in embryos, suggesting that evolution fused two separate nervous systems together hundreds of millions of years ago.
Researchers at Stanford University, led by Kyle Loh, studied early-stage mouse embryos and identified two distinct populations of progenitor cells. One type expresses a gene called OTX2 and gives rise to neurons in the forebrain and midbrain, which govern higher-level thought. The other expresses GBX2 and becomes the hindbrain, the region that controls breathing, sleeping, eating, and heart rate.
«Our research suggests that evolution took two existing neural systems and pushed them together spatially,» 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.»
The team then replicated the finding using human cells in a dish, confirming that human hindbrain neurons also arise from a different progenitor cell than those in the forebrain and midbrain. «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,» Loh said.
The discovery helps explain a long-standing frustration in neuroscience: growing human hindbrain tissue in the lab has proven extraordinarily difficult. According to Loh, researchers had been trying to produce hindbrain neurons from progenitor cells destined for the forebrain and midbrain, an approach that simply does not work. «It was actually a summer student's failed experiment that got us into this,» he said.
With the correct progenitor cell identified, the team successfully grew functional human hindbrain motor neurons in a dish for the first time. That advance could accelerate research into conditions such as amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, and spinal muscular atrophy, both of which affect the hindbrain and cause speech and swallowing difficulties.
The finding may also shed light on how popular GLP-1 drugs like Ozempic and Wegovy work. Scientists recently discovered that these medications suppress appetite in mice by acting on the hindbrain. Having lab-grown human hindbrain neurons should allow researchers to investigate the precise mechanisms of these drugs in people, Loh said.
The evolutionary roots of this split appear to run deep. The researchers examined early-stage embryos of chickens, zebrafish, and acorn worms and found that their nervous systems are similarly derived from two different progenitor cell types. This suggests the two-origin brain system arose at least 550 million years ago.
Jellyfish, which diverged from our lineage roughly 600 to 700 million years ago, possess two separate nervous systems. According to Loh, these may have merged in our distant ancestors because proximity improved overall processing power. «You get more efficient communication when things are closer together,» he said.
The arrangement may also have paved the way for complex thought. While the hindbrain managed basic life-sustaining functions, «evolution could play around with the forebrain, and make mistakes and give rise to all the fancy things like memory and creativity,» Loh said.
The study, published in Nature Neuroscience, offers a new framework for understanding brain development and disease, and raises the possibility that the human brain's dual origins are not a quirk of biology but a fundamental feature inherited from some of the earliest animals on Earth.