Stem-cell breakthrough produces human hindbrain motor neurons

Researchers have produced functional human hindbrain motor neurons from stem cells after identifying a previously overlooked split in early brain development. The advance could give scientists a way to study the nerve cells involved in swallowing, facial movement and breathing—functions that are progressively lost in spinal muscular atrophy and amyotrophic lateral sclerosis.

SciTechDaily reports that the Stanford Medicine-led team traced the cells back to a distinct embryonic route rather than trying to convert progenitors destined to form other parts of the brain. The findings were published in Nature Neuroscience on 18 September 2026.

The lab-grown neurons generated action potentials, the electrical impulses used by nerve cells to communicate. They also made proteins associated with hindbrain areas that control muscles in the face and throat, suggesting that the cells had acquired key features of their natural counterparts.

A separate route to the hindbrain

The researchers began with human pluripotent stem cells, which can develop into many different cell types. To determine how to direct them toward the hindbrain, graduate researchers Rayyan Jokhai and Carolyn Dundes examined gastrulation, an early phase of embryonic development when the body’s basic arrangement emerges.

For much of modern developmental biology, scientists assumed that the forebrain, midbrain and hindbrain emerged from one shared population of precursor cells. The Stanford team’s work challenges that model. In developing mouse embryos, it found two non-overlapping groups instead.

Cells carrying the gene Otx2 developed into the forebrain and midbrain. A separate population marked by Gbx2 became the hindbrain. The two groups were already distinct at the earliest stages examined, with the hindbrain-forming cells developing alongside, rather than from, the cells that generated the front of the brain.

The difference was also visible in chromatin, the molecular packaging that controls which sections of DNA are available for use. The embryonic tissue that gives rise to the forebrain and midbrain had a different chromatin arrangement from the tissue that forms the hindbrain. That distinction helps explain why earlier attempts to grow hindbrain neurons had been unsuccessful: they began with precursor cells committed to another developmental fate.

By following the Gbx2-associated route, the team was able to generate the desired human neurons in the laboratory. Access to such cells is important because brainstem tissue cannot be collected from living patients, leaving researchers with limited ways to observe how disease damages these vulnerable neurons.

Relevance to SMA and ALS

SMA is a major inherited cause of death during the first year of life. ALS is more commonly diagnosed between 40 and 70 and can damage motor neurons in both the hindbrain and forebrain. Although the diseases differ, both can progressively disrupt hindbrain cells that coordinate swallowing and breathing.

When swallowing fails, food or liquid may enter the lungs and lead to pneumonia. As the disease advances, patients can also lose the ability to breathe independently. A human-cell model could allow researchers to examine the earliest changes in affected neurons, test potential treatments and investigate whether damaged cells can be replaced or repaired.

The researchers plan to study precisely how SMA and ALS harm hindbrain motor neurons. They also intend to investigate the developmental origins of the spinal cord. The work may have implications beyond motor-neuron disease, since the hindbrain helps regulate hunger and contains circuits targeted by weight-loss medicines such as semaglutide.

Clues to the brain’s deep history

The developmental discovery also prompted an evolutionary question: if the front and back of the brain arise from separate embryonic populations, might they represent ancient nervous systems that were later joined?

The team found evidence for the same two-origin pattern in chickens, zebrafish and acorn worms, drawing on more than 550 million years of evolutionary history. Acorn worms are distant relatives of humans. Jellyfish, whose lineage diverged from the human line roughly 600 million to 700 million years ago, have nervous systems located at separate ends of their bodies.

The researchers interpret these comparisons as evidence that the modern brain may combine two older neural systems that evolved independently and were later brought together. The result is a single organ whose front and back now work closely as one, while retaining distinct developmental foundations.

The study was supported by the National Institutes of Health, National Science Foundation, California Institute for Regenerative Medicine and several academic, charitable and biomedical organisations, including the Spinal Muscular Atrophy Foundation and the Howard Hughes Medical Institute.