Surprise! You Have Two Brains.

4 min readHere’s what you’ll learn when you read this story:Scientists have long considered the brain to be a single organ, but new research has found that it actually consists of two distinct organs, the forebrain and hindbrain (or brain stem).It turns out that distinct genes assign each cell group to the forebrain or hindbrain within days of embryonic development.The discovery could open treatment paths for once-untreatable neurodegenerative diseases like spinal muscular atrophy (SMA) and ALS.What do humans have in common with mice, chickens, zebrafish, and acorn worms burrowing through ocean sediment?In every one of them, the brain—or its evolutionary equivalent—is built from two separate populations of cells that split apart at the very start of development. Neuroscientists had long treated the human brain as a single organ arising from a single pool of precursors. But new research suggests it’s closer to a composite, because the forebrain and the hindbrain were never quite the same tissue.Researchers Rayyan Jokhai and Carolyn Dundes of Stanford University discovered how this occurs in mice. In a mouse embryo, the cells that will eventually build the brain start out pluripotent, able to become any cell type in the body. They don’t stay that way for long. Within days, during a reshuffling process called gastrulation, that flexibility narrows. The cells split into two separate groups, one assigned to the forebrain, the other to the hindbrain. What divides them is chromatin, the bundle of DNA and proteins that determines which genes a cell is able to switch on.“We postulate the brain is a composite organ emanating from two lineage-restricted progenitors; these dual progenitors may be evolutionarily conserved across 550 million years from hemichordates to mammals,” Jokhai and Dundes said in a study recently published in Nature Neuroscience.The split happens during gastrulation, the early upheaval in which a single sheet of epithelial cells reorganizes into a layered embryo consisting of ectoderm, mesoderm, and endoderm, the three germ layers that produce the body’s tissues. The ectoderm is the one that yields skin and nervous system, and within it sits the neural ectoderm, the tissue set aside for the brain and spinal cord.Embryologists have known for a long time that this tissue comes in an anterior and a posterior type. What they didn’t know was how deep the difference ran. The cells looked identical, so the two domains were understood to be different areas of one developing organ. The Stanford team found the opposite. The chromatin in each domain—the DNA-and-protein packaging that governs which genes are reachable—has already been configured to leave only one path open. Anterior cells can build a forebrain. Posterior cells can build a hindbrain. But the resemblance was skin-deep the whole time.The question had been hard to settle, because nobody could grow the cells in question. Hindbrain progenitors, in particular, had never been produced in a lab. Dundes, Jokhai, and senior author Kyle Loh managed it, though, deriving both populations separately and showing that each one switches on its own transcription factor, a protein that binds specific stretches of DNA and switches other genes on or off.Epithelial cells that give rise to the anterior neural ectoderm express the gene Otx2, which essentially encodes a transcription factor. Epithelial cells build the forebrain and midbrain, which are the regions that make us capable of higher functions like thinking, learning, abstract reasoning, memory, emotional regulation, and sensory processing. Hindbrain cells had never been grown in a lab before. Cells that give rise to the posterior neural ectoderm express a different gene, Gbx2, whose transcription factor targets a different set of DNA sequences. These then become the hindbrain, which regulates vital functions such as breathing, heart rate, blood pressure, sleep, and consciousness—the baseline wakefulness everything else depends on.The pattern reaches further back than vertebrates. Acorn worms, which last shared an ancestor with us some 550 million years ago, sort their neural tissue into anterior and posterior domains the same way, which is what led the authors to call this arrangement “evolutionarily conserved.” Even jellyfish, which split from our lineage 600 to 700 million years ago and never evolved a brain at all, concentrate their nervous tissue at opposite ends of the body. In animals with heads, the two domains ended up packed into the same small space, which may be why the division went unnoticed for so long.Making hindbrain progenitor cells in the lab may also lead to new treatments for currently incurable diseases like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), because the motor neurons these diseases destroy descend from the posterior lineage. The hindbrain is also where semaglutide and related GLP-1 drugs act on appetite, so growing hindbrain progenitors in a lab could make it easier to find new forms of those medicines.“Separate anterior and posterior ectoderm populations arise during gastrulation across deuterostome species as diverse as acorn worm, zebrafish, chicken, mouse and primate,” the researchers said. “We conclude that the emerging notion of two parallel brain progenitors has a number of ramifications for development, differentiation and evolution.”Elizabeth Rayne is a creature who writes. Her work has appeared in Popular Mechanics, Ars Technica, SYFY WIRE, Space.com, Live Science, Den of Geek, Forbidden Futures and Collective Tales. She lurks right outside New York City with her parrot, Lestat. When not writing, she can be found drawing, playing the piano or shapeshifting.