Human brain evolved by fusing two ancient nervous systems, study finds

Stanford researchers led by Kyle Loh have found that the front and back of the vertebrate brain grow from two genetically distinct progenitor cell types in the embryo, rather than from a single shared lineage as previously assumed. In mouse embryos, one population expresses the gene OTX2 and gives rise to forebrain and midbrain neurons, while a separate population expresses GBX2 and builds the hindbrain. Experiments on human cells in culture confirmed the same two-origin split, implying that our brain is effectively two primitive nervous systems that were pushed together spatially hundreds of millions of years ago.

The finding resolves a long-standing lab problem: attempts to grow human hindbrain tissue had failed because researchers were starting from forebrain-destined progenitors. Using the correct GBX2-lineage cells, the team grew functional human hindbrain motor neurons in a dish for the first time. Because the hindbrain governs breathing, heartbeat, sleep, and eating, and is the site of damage in ALS and spinal muscular atrophy, the technique could accelerate motor-neuron disease research and clarify how GLP-1 drugs such as Ozempic and Wegovy act on the brain to suppress appetite.

Comparative work on chick, zebrafish, and acorn worm embryos showed the same dual-progenitor pattern, pushing the origin of this architecture back at least 550 million years. Jellyfish, which diverged earlier and still carry two separate nervous systems, hint at where the split predates the merger. Loh suggests that packaging the two systems together improved processing efficiency and, by offloading survival functions to the hindbrain, freed the forebrain for evolutionary experimentation that produced memory, creativity, and higher thought.