Scientists thought the human brain began as one: New study reveals two ancient cell pathways emerge early, raising a surprising question about how our most complex organ forms

The human brain is usually thought of as one extraordinary organ, a single command centre responsible for everything from breathing and heartbeat to language, memory and imagination. But scientists have now found that it may not have such a simple beginning.

A new study suggests that the brain starts developing from two different groups of early cells, each following its own path before eventually becoming parts of the same organ. One group goes on to form the front and middle portions of the brain, while the other produces the hindbrain, the region involved in some of the body's most basic survival functions.

The finding, led by researchers at Stanford Medicine and published in Nature Neuroscience, could change how scientists understand the earliest stages of brain development, and may help solve a problem that has hampered research into serious neurological diseases.

The brain's surprising two-part beginning

To understand the discovery, it helps to go back to a stage of pregnancy long before a recognisable brain exists. During a very early phase of embryo development called gastrulation, cells begin organising themselves into the different tissues that will eventually make the body.

Researchers studying mouse embryos discovered that two separate groups of cells were already being set aside for different parts of the future brain.

One group was destined to form the forebrain and midbrain. These areas are involved in functions such as thinking, processing information and conscious behaviour.

The other group was destined to become the hindbrain. This region contains neural circuits involved in automatic functions that we perform without consciously thinking about them, including breathing and regulating the heartbeat. It also helps control muscles involved in swallowing, facial movements and speech.

In simple terms, scientists found that the cells that eventually make the front of the brain and those that make the back of the brain are not simply different versions of the same starting cells. They begin on separate developmental routes remarkably early.

Why this changes what scientists thought

The researchers found that the two groups also behaved differently at the molecular level. The forebrain-and-midbrain cells carried a gene called Otx2, while the future hindbrain cells expressed Gbx2. The DNA inside the two groups was also packaged differently.

That packaging matters because DNA contains thousands of genes, but cells do not use all of them. The way DNA is packaged helps determine which genetic instructions a cell can access.

The researchers' results suggest that these two groups become committed to their different futures very early. That discovery may explain why scientists have struggled to make certain hindbrain cells from stem cells in the laboratory.

For years, researchers have tried to persuade stem cells to become specific types of neurons. But if they begin with cells that are already headed toward a forebrain or midbrain identity, simply adding new chemical signals later may not turn them into hindbrain cells.

The Stanford team took a different approach: they recreated the earlier developmental stage first. Using human pluripotent stem cells, capable of producing many different cell types, the researchers generated the appropriate early cells and successfully developed them into functional hindbrain motor neurons.

The neurons produced electrical signals and showed molecular features expected of genuine hindbrain cells, according to the study.

A possible breakthrough for brain disease research

This matters because some devastating neurological diseases affect precisely these kinds of neurons. In spinal muscular atrophy (SMA), certain motor neurons progressively stop working. ALS can also damage motor neurons, eventually affecting a person's ability to move, swallow and breathe.

Studying these diseases directly in living human brain tissue is extremely difficult. Scientists therefore rely heavily on laboratory-grown cells and other models.

Being able to produce the relevant hindbrain neurons more accurately could give researchers a new way to investigate how these diseases develop and test potential treatments, Stanford Medicine reported.

The finding could also help scientists study other functions controlled by the hindbrain, including circuits involved in hunger and swallowing.