For decades, the prevailing model of neurobiology held that the entire human brain originated from a single, unified progenitor cell population. However, a study led by Stanford Medicine researchers, published in Nature Neuroscience on September 18, 2026, challenges this view by demonstrating that the brain is composed of two distinct, ancient nervous systems that develop in parallel. By examining mouse embryos, the team identified two mutually exclusive progenitor cell populations: one expressing the Otx2 gene, which forms the forebrain and midbrain, and another expressing the Gbx2 gene, which is committed to forming the hindbrain. These populations are locked into their respective fates by fundamentally different chromatin configurations, which determine gene accessibility. This developmental split explains why previous attempts to generate hindbrain neurons in the laboratory—often by attempting to coax forebrain progenitors into hindbrain cells—have frequently failed. By understanding these distinct origins, the researchers successfully coaxed human pluripotent stem cells into functional hindbrain motor neurons. These lab-grown neurons exhibit characteristic electrical activity and protein production, providing a new tool for investigating diseases that affect the brain stem, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). The researchers observed this dual-origin pattern across various species, including chickens, zebrafish, and acorn worms, suggesting that the brain evolved as two separate pieces that were later packaged together.
The research highlights that the brain is composed of two distinct, ancient nervous systems that develop in parallel, rather than originating from a single progenitor cell population.