Stanford Study Finds Human Brain Is Actually Two Organs

For centuries, the brain has been considered a single, unified organ. New research led by Stanford Medicine shows instead that what is called the brain is actually two distinct organs that evolved independently over hundreds of millions of years. The finding overturns the prevailing model of brain development, which held that a single progenitor cell early in development gives rise to the entire brain. Instead, the human brain consists of two ancient nervous systems packaged together: a more primitive part that regulates heartbeat, breathing and other automatic functions, and another that supports distinctly human capacities such as language and abstract reasoning.

The adult brain has three main regions: the forebrain, midbrain and hindbrain. The forebrain handles higher-level thinking, while the hindbrain, or brain stem, controls essential functions including breathing, sleeping, heartbeat and hunger, along with muscles of the face, tongue and throat that affect speech and swallowing. Scientists have struggled for decades to generate human hindbrain neurons in the laboratory, a gap that has hampered research into diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS).

The breakthrough came from studying embryonic development during gastrulation. Rayyan Jokhai and Carolyn Dundes, co-first authors of the study published in Nature Neuroscience, found that the hindbrain follows a separate developmental path running parallel to, rather than branching off from, the pathway that forms the forebrain and midbrain. Examining mouse embryos, the researchers identified two distinct progenitor cells—one expressing the gene Otx2, destined to become the forebrain and midbrain, and another expressing Gbx2, committed to forming the hindbrain—that never overlap. Differences in chromatin configuration locked each progenitor cell into its respective fate.

“Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” Jokhai said.

Using this knowledge, the team successfully coaxed human pluripotent stem cells into functional hindbrain motor neurons in the lab for the first time. Looking back over 550 million years of evolutionary time, the researchers found the same two-origin pattern in chickens, zebrafish and acorn worms.

“Our research suggests that evolution took two existing neural systems and pushed them together spatially,” said senior author Kyle Loh.

The findings open new possibilities for studying SMA, ALS and hindbrain circuits involved in hunger regulation, including how weight-loss drugs like semaglutide work.