A new study led by Stanford Medicine researchers has challenged the long-held understanding of how the human brain develops, finding that it originates from two distinct populations of early progenitor cells rather than a single developmental source.The researchers say their findings suggest that the human brain is essentially a composite structure formed from two ancient nervous systems that evolved independently and were eventually integrated into one organ. The study was published in Nature Neuroscience on September 18, 2026.For decades, scientists had followed a model in which a single early progenitor cell was thought to give rise to the entire brain. The new research instead found that the forebrain and midbrain arise from one progenitor population, while the hindbrain develops from another distinct population.“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, associate professor of developmental biology at Stanford Medicine.
Two developmental origins
The adult brain consists of the forebrain, midbrain and hindbrain. The forebrain is responsible for higher-level functions including language, consciousness and abstract reasoning, while the hindbrain controls essential automatic processes such as breathing, sleep, heartbeat and hunger. It also helps control muscles involved in facial movement, speech and swallowing.The Stanford team found that these regions follow different developmental paths from the earliest stages of embryonic development.Researchers studying developing mouse embryos identified two distinct progenitor populations. Cells expressing the Otx2 gene were destined to form the forebrain and midbrain, while cells expressing Gbx2 were committed to forming the hindbrain. The two populations remained separate rather than one developing from the other.According to the researchers, this could explain why scientists have struggled for years to produce certain types of hindbrain neurons in the laboratory.“Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” said Rayyan Jokhai, a co-first author of the study.
Scientists successfully grew hindbrain neurons
The discovery also produced a practical breakthrough. Using human pluripotent stem cells, the researchers were able to generate functional hindbrain motor neurons in the laboratory.The cells showed characteristics of genuine hindbrain neurons, including electrical activity and proteins associated with regions controlling facial and swallowing muscles.Loh said the discovery means researchers can now grow neurons from the hindbrain in a laboratory setting and study how they function.This could be particularly important for research into neurological disorders that affect the brain stem, including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Researchers have historically struggled to obtain and study relevant hindbrain neurons, making laboratory models difficult to develop.
The finding stretches back 550 million years
The researchers also examined the evolutionary history of the nervous system and found evidence that the two-origin pattern extends across roughly 550 million years of evolution.The pattern was identified in species including chickens, zebrafish and acorn worms, which are distant relatives of humans. The researchers said this suggests the developmental arrangement is deeply conserved across evolution.“Our research suggests that evolution took two existing neural systems and pushed them together spatially,” Loh said. He added that although having one developmental origin might appear more efficient, humans have retained this ancient arrangement in which the brain develops from two separate systems.Jokhai said the findings were surprising because the word “brain” naturally suggests a single organ with a single origin.“But even 500 million years ago, there were these separate neural systems, which now almost operate as one,” he said.
What the discovery could mean for disease research
The researchers believe the new developmental model could help scientists better understand diseases affecting the brain stem and potentially develop new approaches to studying them.The ability to grow functional hindbrain neurons in the laboratory gives researchers a way to investigate how disorders such as SMA and ALS affect these cells without needing tissue from living patients. Stanford Medicine said the work could eventually support research into regenerative therapies.The team now hopes to investigate the developmental origins of the spinal cord and better understand how diseases such as SMA and ALS disrupt hindbrain neurons.The study does not mean that humans literally have two anatomically separate brains. Rather, it challenges the traditional idea that the entire brain develops from a single progenitor population and provides evidence that two distinct developmental systems come together to form the brain.
