New study suggests the brain may be two nervous systems merged

A new study from Stanford researchers challenges a core idea about how the brain forms in the embryo, showing that two separate groups of progenitor cells contribute to different brain regions. The finding could change how scientists model brain development in the lab and help researchers grow cell types linked to movement and vital reflexes.

Two developmental origins

Traditionally, the brain is described as a single organ that divides into the forebrain, midbrain and hindbrain, each performing distinct roles in cognition, sensation and bodily control. The new research suggests those regions arise from two distinct populations of early embryonic cells that follow separate developmental paths.

Studying mouse embryos at the gastrulation stage — when cells begin organizing into the tissues that form organs — the team identified one cell group that expresses the gene Otx2 and a second that expresses Gbx2. The Otx2-expressing cells go on to form much of the forebrain and parts of the midbrain, while Gbx2-marked cells give rise to hindbrain structures and the remainder of the midbrain.

These populations maintained distinct identities as they matured. The researchers also analyzed chromatin — the DNA-packaging structure that influences which genes a cell can access — and found different chromatin configurations in the two groups. That molecular difference supports the idea of parallel developmental programs rather than a single, continuous lineage.

“The brain appears as one organ,” said study co-author Kyle Loh, an associate professor of developmental biology at Stanford University. “However, we discovered that the front part of the brain and the back part of the brain come from different sources, which are pushed together to create the appearance of a single organ,” Loh told Live Science in an email.

Lab-grown cells and a long-standing obstacle

For years, scientists have struggled to produce authentic hindbrain neurons in cell-culture systems. The paper argues this may be because previous methods attempted to convert forebrain or midbrain progenitors into hindbrain cells — a process the new results suggest is fundamentally limited.

“Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” said co-author Rayyan Jokhai, a graduate student in Loh’s lab, in a statement.

Using their developmental map, the researchers then guided human stem cells to become functional hindbrain motor neurons. These lab-grown neurons produced proteins typical of hindbrain motor systems that control facial muscles and swallowing.

Implications for neurological disease

Those motor neurons are affected in several serious disorders. In conditions such as spinal muscular atrophy and amyotrophic lateral sclerosis, patients can lose the ability to swallow, speak or breathe as motor neurons degenerate.

Loh noted that sampling living hindbrain motor neurons from patients is not feasible. Growing them in a dish, he said, provides a new experimental avenue to observe disease mechanisms and test potential therapies.

Deep evolutionary roots

The team also checked whether the dual-origin pattern appears beyond mice. Reanalyzing published datasets from macaques, zebrafish and chickens, they found similar separations of Otx2- and Gbx2-expressing cell populations. Remarkably, the pattern also showed up in data from acorn worms, an invertebrate whose lineage split from vertebrates about 550 million years ago.

“The Stanford discovery establishes that the deep ancestry of the vertebrate brain is fundamentally modular,” said Anna Di Cosmo, a professor of biology at the University of Naples Federico II, who was not involved in the work. “The developmental separation between the anterior lineage (forebrain/midbrain) and the posterior lineage (hindbrain) is traceably ancient,” Di Cosmo told Live Science in an email.

The authors suggest these two developmental trajectories may reflect an ancient arrangement in which separate nervous systems later became juxtaposed and integrated during evolution. They caution, however, that the study does not establish exactly when or how such integration occurred.