Why are the cells so stubborn?

The answer may lie in chromatin — the way DNA is packaged and organized inside cells. The two cell types showed markedly different chromatin arrangements. In anterior cells, forebrain genes were accessible and ready for action, while hindbrain genes were locked away — and vice versa.

Eduardo Sequerra, a researcher at the Brain Institute at the Universidade Federal do Rio Grande do Norte who was not involved in the study, said the key takeaway is "that the neuroectoderm divides into two separate progenitor populations that diverge in their potential to generate different brain regions." Crucially, this split happens "much earlier than the neural tube formation" — the stage when the early embryonic structure that becomes the brain and spinal cord takes shape.

"I am quite confident in their very interesting finding," Sequerra added. "They joined in vivo developmental studies across different species with in vitro differentiation systems to show their hypothesis is solid in different ways."

The work also builds on transplantation studies from the 1990s by Nicole Le Douarin's group, which suggested the folding neural tube was already divided into two parts.

Why does this matter for medicine?

Using their new roadmap, the team directed posterior neural ectoderm cells to grow into specialized hindbrain motor neurons — the cells that control muscles in the face and neck, including those needed for swallowing. The lab-grown neurons showed spontaneous calcium activity and fired electrical impulses when stimulated, signs that they were functional.

"We are excited by the ability to create human hindbrain neurons in a Petri dish," Loh said. The hindbrain, also known as the brainstem, controls life-sustaining functions such as sleep, wakefulness, consciousness, and hunger.

The clinical stakes are high. ALS and spinal muscular atrophy both kill hindbrain motor neurons involved in eating, swallowing, and speech. "In particular, spinal muscular atrophy is the #1 genetic cause of death in babies under 1 year of age," Loh noted.

"We cannot sample living motor neurons from a patient's hindbrain to watch how these diseases attack these neurons," Loh explained. "Growing these hindbrain motor neurons in a dish gives us a way to investigate these diseases." The researchers hope to use this system to discover and test potential treatments.

Sequerra urged caution, though. The approach relies on studying patient-specific cells in a dish — using induced pluripotent stem cells, or iPSCs — rather than replacing damaged tissue in the body. "It definitely is not close to a stem cell therapy for regeneration," he said.

What are the limitations?

Several caveats apply. Growing human cells in a flat plastic dish does not fully recreate the complex, three-dimensional environment of a developing embryo, so the cells might behave slightly differently in isolation. Other, unknown chemical combinations might also exist that could force the cells to switch identities — something that is technically very difficult to test in living mammals.

Loh also stressed that the findings should not be misread as suggesting the brain is two separate organs. "The brain is one organ, but it is built from two different sources," he said. By analogy, the heart's right ventricle comes from one source and its other three chambers from another, yet all four work together.

The researchers also examined embryos of macaques, chickens, zebrafish, and acorn worms — marine worms that are distant relatives of backboned animals — and found distinct anterior and posterior neural cell groups in all of them.

Loh offered one speculative idea, clearly flagged as tentative: early in evolution there may have been no "grand plan" for a single brain. Instead, two separate nervous systems may have existed and later been pushed together into one integrated organ. "It is important to emphasize that this is only an idea, and it might change as scientists learn more," he said.