For centuries, scientists viewed the brain as one unified organ. A new Stanford Medicine study published in Nature Neuroscience on 18 September by lead authors Rayyan Jokhai and Carolyn Dundes overturns that idea. It shows that what we call the brain is really two ancient nervous systems joined together. The front part, which includes the forebrain and midbrain, comes from one type of starter cell. The back part, the hindbrain, comes from an entirely different starter cell. These two cell groups never mix. "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.

To understand the findings, go back to gastrulation, the early stage when an embryo organises into three layers. The outer layer, called ectoderm, forms the skin, hair, teeth and the nervous system. For decades, scientists thought a single type of neural ectoderm cell made the whole brain. The Stanford team, led by Rayyan Jokhai and Carolyn Dundes, examined mouse embryos and found two separate populations. The first is anterior neural ectoderm. 'Anterior' means 'front', toward the head. These cells have a gene called Otx2 switched on. A gene is a section of DNA that carries instructions. When a gene is switched on, it is active. Otx2 acts like a name tag for these cells. This group is destined to become the forebrain and midbrain, which are the front and middle parts of the brain. The second group is posterior neural ectoderm. 'Posterior' means 'back', toward the tail. These cells have a different gene, Gbx2, switched on. Gbx2 acts like a different name tag. This group is destined to build the hindbrain, the back part of the brain that controls breathing, heartbeat, swallowing and other automatic life functions. Otx2 and Gbx2 are not the brain regions themselves. They are molecular labels that help identify the two cell groups and have roles in their development. The two groups never mix. They are like two separate construction crews, one for the front brain and one for the back brain.

Deep Roots

Why can't these cells switch identities? The answer lies in chromatin, the packaging that organises DNA. Think of DNA as a cookbook. Chromatin decides which recipes are open and easy to read and which are sealed shut. The two cell types had different open pages. In anterior cells, forebrain genes were open and easy to read, but hindbrain genes were locked shut. In posterior cells, the opposite was true. The pattern was already set during gastrulation, days before actual brain regions formed. This finding explains why earlier attempts to turn forebrain starters into hindbrain cells failed under the conditions tested. They were trying to turn a train into a boat.

Using this knowledge, the Stanford team grew human hindbrain motor neurons in the lab, including a type that had been difficult to generate. They started with human pluripotent stem cells, which can become almost any cell type. They guided them step by step into the posterior neural ectoderm and then into hindbrain motor neurons. The lab-grown neurons expressed the right genes, made acetylcholine, a chemical messenger used by motor neurons, and fired action potentials, the electrical signals neurons use to communicate. These neurons control face and throat muscles used in swallowing and speech. This is relevant for diseases like amyotrophic lateral sclerosis, or ALS, and spinal muscular atrophy, or SMA, where these neurons fail, and patients lose the ability to swallow and breathe.

The team then looked across evolution. They found the same split in chickens, zebrafish, macaques and even acorn worms, marine creatures that shared a common ancestor with humans over 550 million years ago. This suggests the two-part brain plan is ancient, predating vertebrates – animals with backbones. The pattern is even older than that. Jellyfish, which diverged from our lineage about 600 to 700 million years ago, do not have a brain at all. They have two separate nerve nets, one at each end of the body. The two-part arrangement is not a recent invention. It is a deep feature of animal biology, inherited and retained across vast stretches of evolutionary time. In our distant ancestors, these two separate systems were pushed together spatially probably giving the advantage of efficient communication. There was also a likely second advantage of flexibility due to modularity. Keeping them separate allowed one to evolve new capabilities while the other maintained the status quo. These advantages are still speculative, and further research is needed to test them. But this arrangement has proved remarkably successful. It was retained in fish, amphibians, reptiles, birds, and mammals, including humans. The two systems became so tightly integrated that we experience them as a single brain, but they still develop from separate starter cells and retain their separate identities at the deepest level.

From Nerve Nets to Complex Minds

That raises a bigger question: how did brains evolve? The simplest animals, like sponges, have no nervous system but can send electrical signals. The first true nervous systems were nerve nets, diffuse webs of nerve cells seen in jellyfish. In the evolution of a brain, this marked the initial stage. Complex brains evolved independently many times. Insects such as bees have mushroom bodies, brain regions that support learning, navigation and social behaviour. Octopuses have about 550 million neurons distributed differently from us. But their actions indicate that they can solve puzzles, use tools, and recognise individual humans. Intelligence is not a human monopoly.

Vertebrates evolved a three-part brain: forebrain, midbrain and hindbrain. This plan persists from sharks to humans, though proportions and complexity vary. Mammals added the neocortex, a new outer layer. In humans it constitutes about 80 per cent of brain volume. Early mammals had a small neocortex, but it expanded dramatically in some lineages. Primates, including lemurs, monkeys, apes and humans, evolved from small nocturnal insect-eaters about 80 million years ago. They developed excellent vision and precise hand control for life in trees. As primates evolved, some lineages developed larger brains relative to body size.

The human lineage split from chimpanzees about 6 to 8 million years ago. Early human ancestors had brains about one-third the size of modern human brains. Over the last 2 to 3 million years, the human brain nearly tripled in size. It also reorganised. The prefrontal cortex, behind the forehead, became proportionally larger. The neocortex is divided into more distinct areas. Language regions appeared. The two parts of the brain became specialised for different tasks. These changes accumulated gradually as our ancestors adapted to changing environments, made tools and lived in complex social groups. This is a back-and-forth, dialectical process, between biology and the environment, each shaping the other.

A Branch, Not the Pinnacle

Human brain evolution is not over. A 2026 study published in the journal Nature by Ali Akbari, David Reich and others analysed over 15,000 ancient and modern genomes from Western Eurasia. This large-scale study, one of the most comprehensive of its kind, compared DNA from ancient remains with that of modern people. They found 479 genetic variants that changed over the last 10,000 years. They span traits related to neural development, immunity, blood type, and cardiometabolic health. The shift to farming brought new diets, diseases and social structures, and natural selection responded. Other studies show ongoing selection on genes like ASPM, which is involved in brain size, and on genes linked to neuronal communication. Humans are not getting smarter in a simple sense. Instead, advantageous variants became more common, and harmful ones got removed.

It is tempting to see evolution as a ladder with humans at the top. But evolution is a tree, not a ladder. Every living species is adapted to its environment. Crows can make tools, and magpies can recognise themselves in mirrors. Octopuses' brains are organised completely differently from ours. Their brains solve problems in ways completely different from ours. Humans are one branch on a vast tree, not the pinnacle. The Stanford discovery adds to this view. The human brain itself is a composite organ, two ancient nervous systems fused. One part, the hindbrain, controls basic life support: eating, sleep, wakefulness, heartbeat. The other part enables, now for us modern humans, poetry, mathematics and self-reflection. Both are products of evolution, and both continue to evolve. As Jokhai said, "Now we have a model to better understand devastating diseases and work toward regenerative therapies for them." The brain is not a finished masterpiece. It is a work in progress, one branch among many.