Stanford Study Finds Human Brain Is Two Separate Organs That Evolved Independently
Researchers at Stanford University School of Medicine have determined that the human brain is not a single organ but two distinct organs that evolved independently over hundreds of millions of years, challenging a long-held assumption about embryonic development.
The human brain is not one organ but two, each with a separate evolutionary origin stretching back hundreds of millions of years, according to research from Stanford University School of Medicine published in the journal Nature Neuroscience. The finding overturns the long-standing assumption that the entire brain develops from a single population of precursor cells in the early embryo.
The study identifies two ancient nervous systems operating in the body. One is more primitive and governs heartbeat, breathing and other reflexive functions. The other supports higher cognitive abilities, including speech and abstract thought. Working with mouse embryos at the gastrulation stage, the earliest phase of body formation, the researchers found that the hindbrain, or rhombencephalon, follows its own developmental path, parallel to rather than derived from the path that produces the forebrain and midbrain.
At the centre of the discovery are two groups of precursor cells. One expresses the gene Otx2 and goes on to form the forebrain and midbrain. The other expresses Gbx2 and builds the hindbrain. These cell populations never intersect, even from the earliest stages of development. The front of the brain, in other words, arises from an entirely different precursor cell than the back.
The implications reach well beyond developmental biology. According to the researchers, the finding explains why scientists spent decades failing to grow hindbrain neurons in the laboratory. Earlier attempts tried to convert forebrain and midbrain precursor cells into hindbrain cells, an approach the study shows to be impossible in principle. With the new understanding, the team succeeded for the first time in coaxing human stem cells to become functional motor neurons of the hindbrain. These cells displayed electrical activity and produced proteins characteristic of the hindbrain segments that control the muscles of the face and swallowing.
That advance opens new avenues for studying spinal muscular atrophy and amyotrophic lateral sclerosis, or ALS, diseases in which hindbrain neurons progressively fail, eventually robbing patients of the ability to swallow and breathe. The researchers traced the same two-component pattern of brain formation back some 550 million years, finding it in chickens, zebrafish and sea acorns, bottom-dwelling ocean creatures that share a distant ancestor with humans. In jellyfish, which split from the human evolutionary line 600 to 700 million years ago, the two nervous systems sit at opposite ends of the body.
The work adds a new dimension to the story of the Cambrian explosion, the period when the diversity of living things on Earth expanded dramatically. If the brain is better understood as two organs with separate histories, that division may have deep roots in the evolutionary innovations that made complex animal life possible. For now, the study offers both a revised map of how the human brain is built and a practical tool: a reliable way to produce hindbrain neurons in the laboratory for research into diseases that currently have few answers.
