Scientists Discover Two Separate Cell Populations That Build the Brain

New research is challenging the long-held idea that the brain develops from a single origin. Instead, the brain may arise from two distinct populations of cells that follow separate developmental pathways before forming one organ.

“The brain looks like one organ,” said study co-author Kyle Loh, associate professor of developmental biology at Stanford University. “But we found that the front part of the brain and the back part of the brain come from different sources, and together they create the appearance of a single organ.”

The findings, published in Nature Neuroscience in September 2026, could help explain why scientists have struggled to grow certain types of brain cells in the laboratory. The discovery may also provide a new way to study diseases that affect the brainstem, the structure connecting the brain to the spinal cord.

Two developmental pathways shape the brain

The human brain is divided into three main regions: the forebrain, midbrain and hindbrain. These areas perform different but interconnected functions.

The forebrain includes the cerebral hemispheres and supports higher cognitive processes such as language, planning and abstract thinking. The midbrain sits at the top of the brainstem and helps relay sensory information while controlling movement. The hindbrain includes the base of the brainstem and structures involved in movement, breathing, sleep and heart rate.

Studying the hindbrain has been difficult because researchers have faced continuing challenges in generating functional hindbrain neurons in the laboratory.

To investigate why, Loh and his team examined the early stages of embryonic development in laboratory mice. They focused on gastrulation, the stage when cells begin organizing into structures that will later form various organs.

The researchers identified two distinct populations of immature cells that contribute to nervous system tissue, including the brain.

One population expressed the OTX2 gene, which helps direct early development of the forebrain and midbrain. The other expressed the GBX2 gene, which is involved in midbrain and hindbrain development.

Although the functions of these genes were already known, the study revealed that they are expressed differently in the two cell populations. Rather than merging early in development, the populations remained distinct until they formed mature neural tissue.

The team also examined chromatin, the molecular structure that packages DNA inside the nucleus and helps control which genes a cell can use. The two cell populations showed different patterns of chromatin organization, further supporting the idea that they follow separate developmental pathways.

Why the discovery matters for brain research

The findings may explain why previous attempts to grow hindbrain neurons have had limited success. According to the researchers, scientists may have tried to turn forebrain and midbrain progenitor cells into hindbrain cells even though the two cell populations originate separately.

“Previous attempts to generate hindbrain neurons have likely attempted to direct forebrain and midbrain progenitor cells into hindbrain cells, but our study shows that this is not possible,” said Rayan Jokai, a graduate student in Loh’s lab, in a statement.

Using the information from the mouse experiments, the researchers successfully guided human stem cells to form functional hindbrain motor neurons involved in movement. The cells produced proteins characteristic of the hindbrain, including the region that helps control facial muscles and the muscles used for swallowing.

Motor neurons deteriorate in neurological diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis. As these neurons are damaged, patients may lose the ability to swallow, speak and breathe independently.

“We can’t take living motor neurons from a patient’s hindbrain and see how these diseases attack these neurons,” Loh said. “Cultivating these hindbrain motor neurons in a dish gives us a way to study these diseases.”

The team hopes to use the lab-grown neurons to investigate these conditions and identify potential treatments.

Evidence of an ancient evolutionary pattern

The researchers also investigated whether the two developmental pathways are unique to humans or reflect an older evolutionary mechanism. They examined previously published data from other species, including macaque monkeys, zebrafish and chickens, and again found two distinct cell populations expressing the two important genes.

The researchers also identified the two cell groups in acorn worms, marine invertebrates that evolved from vertebrates about 550 million years ago.

“Stanford University’s findings demonstrate that the deep ancestry of vertebrate brains is fundamentally modular,” said Anna Di Cosmo, a professor of biology at the University of Naples Federico II who was not involved in the study.

“The developmental separation between the anterior lineage—forebrain and midbrain—and the posterior lineage—hindbrain—is clearly ancient,” Di Cosmo told Live Science.

The researchers speculate that the two developmental pathways may reflect a time when the cell populations belonged to two separate nervous systems. Later in evolution, the two systems may have been brought together, creating a unified brain.

However, the study does not reveal when the two pathways first arose or how they were integrated. The researchers emphasize that the evolutionary explanation remains an idea that could change as scientists learn more.

Study details

Jokai, R. T., Dandes, C. E., Ahsan, H. S., et al. (2026). “Two parallel neuroectodermal progenitor cells contribute to brain development.” Nature Neuroscience.

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