The Human Brain... Two Separate Organs!
For centuries, scientists regarded the brain as a single, integrated organ. However, a research study led by Stanford University School of Medicine concluded that what we call the brain is actually two distinct organs that evolved independently over hundreds of millions of years. This discovery overturns a model that has prevailed for decades, which assumed the existence of a single progenitor cell at the beginning of development from which all parts of the brain arise.
According to the study, published in the journal Nature Neuroscience, the human brain consists of two ancient nervous systems that were joined together: a more primitive part that regulates heartbeat, respiration, and other functions, and another that distinguishes humans, enabling them to engage in poetry, mathematics, and contemplation of their origins. Dr. Kyle Lu, the study’s lead author and associate professor of developmental biology, explained that the team proved for the first time that the forebrain arises from a progenitor cell that is entirely different from the one that gives rise to the hindbrain.
The adult human brain comprises three regions: the forebrain, midbrain, and hindbrain. The forebrain is responsible for higher-order thinking, such as language, consciousness, and abstract reasoning. The hindbrain, located at the back of the skull, regulates automatic vital functions like breathing, sleep, heartbeat, and hunger drives. Its nerve cells also control the muscles of the face, tongue, and throat, which are essential for speech and swallowing.
This research breakthrough stemmed from an initial study of early embryonic development during gastrulation, when the body begins to take shape. The study’s co-first authors, Caroline Dendys and Ryan Goukhai, discovered that the hindbrain follows a separate developmental trajectory parallel to that of the forebrain and midbrain, rather than branching off from them. Examination of mouse embryos revealed the following:
Goukhai noted that previous attempts likely tried to push progenitor cells of the forebrain and midbrain into transforming into hindbrain cells, a process the study proves is impossible. Based on this knowledge, researchers succeeded for the first time in directing human pluripotent stem cells to become functional motor neurons of the hindbrain. These neurons exhibited waves of electrical activity known as action potentials and produced proteins characteristic of hindbrain regions that control the muscles involved in facial movement, speech, and swallowing.
Looking back 550 million years of evolution, the team found the same dual-origin pattern in chickens, zebrafish, and acorn worms—small creatures living on the ocean floor that share a distant common ancestor with humans. The study noted that jellyfish, which diverged from humans 600 to 700 million years ago, possess two nervous systems located at opposite ends of their bodies. Lu explained that evolution likely drove two existing nervous systems to converge spatially, adding that while having the brain as a single organ may be more efficient, organisms have retained this primitive arrangement.
These findings open new avenues for studying brainstem diseases. Spinal muscular atrophy is one of the leading genetic causes of death in children under one year of age, while amyotrophic lateral sclerosis (ALS) is typically diagnosed between the ages of 40 and 70 and affects both the forebrain and hindbrain. In both diseases, specific nerve cells in the hindbrain gradually cease to function, causing patients to lose the ability to swallow, which can lead to pneumonia and eventually loss of respiratory function. Previously, researchers were unable to obtain brainstem tissue from living patients, making the study of these diseases nearly impossible.
The study also revealed an unexpected link to obesity treatment, as the hindbrain region contains circuits that regulate hunger, which is the mechanism through which weight-loss drugs such as semaglutide work. Joxai expressed that researchers now have a model for understanding these diseases and working toward regenerative therapies. The team plans to expand its studies to identify the developmental origins of the spinal cord and determine how these two diseases disrupt the function of hindbrain cells, in collaboration with researchers from the California Institute of Technology and the University of California, San Francisco.
