Your Brain Is Actually Two Ancient Organs That Fused Together

A Fundamental Rethink of How the Brain Forms

For centuries, scientists assumed the human brain developed from a single ancestral pool of cells — one origin story, branching out into the complex organ we carry in our skulls. A landmark new study from Stanford Medicine has turned that assumption on its head. The brain is two separate organs that work together, rather than a single unified unit. The research, published in Nature Neuroscience, rewrites a foundational chapter of biology.

A Stanford-led research team says the brains of humans and other animals are actually made up of two collaborating neural systems that start developing in parallel in an embryo's earliest moments. The study found that different brain regions arise from separate kinds of embryonic cells known as progenitors — one cell type leads to the development of the forebrain and midbrain, while another goes on a totally different path to form the hindbrain. The two cell populations never overlap.

What Each Half of Your Brain Actually Does

The forebrain handles higher-level thinking — language, consciousness, and abstract reasoning. In contrast, the hindbrain, located at the back of the skull and often called the brain stem, controls essential, automatic functions that keep us alive: breathing, sleeping, and regulating our heartbeat and hunger urges. The hindbrain neurons also control the muscles of the face, tongue, and throat, which affect speech and swallowing.

Researchers now think that at some point in human evolutionary history, the two parts of the brain may have been separated in space — similar to how jellyfish have two nervous systems in different parts of their body — before moving together. The human brain, therefore, consists of two ancient nervous systems "cleverly packaged together" and evolved independently over millions of years. The progenitor cells that create the fore- and midbrain produce a specific protein using a gene called Otx2, while the soon-to-be hindbrain cells express a gene called Gbx2. Both kinds of progenitor cells form the basis for the complete organ that is our brain, but their roles are not interchangeable. The way their DNA is packaged is fundamentally different too, with totally distinct chromatin landscapes.

Why This Solves a Decades-Long Laboratory Mystery

Despite the critical importance of the hindbrain, scientists have struggled for decades to generate human hindbrain neurons in the laboratory. Now, researchers know why: they were working from the wrong biological blueprint. The anterior and posterior neural ectoderm exhibit fundamentally distinct chromatin configurations from early gastrulation, explaining why decades of attempts to coax forebrain precursors into hindbrain tissue failed.

Armed with knowledge of how hindbrain cells uniquely form, the team successfully turned human stem cells into functional hindbrain motor neurons in a lab for the first time. For researchers, the ability to produce these specific nerve cells is expected to dramatically accelerate research into fatal neurodegenerative conditions like ALS and spinal muscular atrophy (SMA), which specifically target and destroy motor neurons in the lower brain.

A Separate ALS Breakthrough Offers Real Hope for Patients

The Stanford findings arrive alongside another encouraging development in the fight against ALS. A man with an uncommon type of motor neuron disease experienced improved symptoms and continued to work as a physician a year after becoming the first person to receive a drug designed to target the specific genetic mutation that causes his disease. The man had a slowly progressing form of ALS caused by a rare mutation that leads to protein build-up contributing to the death of motor neurons. He received an RNA treatment called antisense oligonucleotide therapy, which uses short strands of genetic material to target RNA produced by the gene and reduce how much protein is made.

Treatment markedly reduced plasma neurofilament light concentrations — a biomarker of neurodegeneration — and stabilized pulmonary function, cognitive performance, and physical abilities. Antisense therapies have been developed to target more common gene mutations that cause ALS, but those therapies took at least a decade to make. By contrast, the drug that targets the CHCHD10 mutation took only three years to develop. Neurologist and ALS researcher Steve Vucic of the University of Sydney calls the results an "exciting first step," though he cautions it is too early to know whether the treatment could stop disease progression or serve as a cure. Taken together, these two breakthroughs — one redefining how the brain is built, the other showing a personalized RNA drug can ease a fatal disease — suggest neuroscience is entering a remarkably productive era, with the hardest problems finally beginning to yield.