This two-origin model explains past difficulties in generating hindbrain neurons in the lab and enables the production of functional hindbrain neurons from pluripotent stem cells for study and potential therapies.

Researchers identified two distinct progenitor cell groups in developing mouse embryos: one giving rise to the forebrain and midbrain, associated with reasoning, language, and consciousness, and a second giving rise to the hindbrain, which controls breathing, heartbeat, swallowing, sleep, and facial movements.

A Stanford Medicine-led study proposes that the human brain originated from two independent neural ectoderm progenitor populations, suggesting two ancient nervous systems rather than a single, continuous organ.

During gastrulation, Otx2-expressing cells were fated for the forebrain/midbrain while Gbx2-expressing cells formed the hindbrain, with these lineages remaining distinct due to different chromatin configurations.

Scientists successfully produced functional human hindbrain motor neurons from stem cells, displaying hindbrain characteristics and activity related to muscles used in facial movements and swallowing.

The study demonstrates hindbrain neurons can be generated in vitro and exhibit action potentials and hindbrain-specific markers, offering a breakthrough for research into motor neuron diseases.

In the brain, the hindbrain governs automatic functions such as breathing, heartbeat, and swallowing, while the forebrain/midbrain handles higher-level processes like language and abstract thinking.

Reference: Jokhai RT et al., Two parallel neural ectoderm progenitors contribute to the developing brain, Nat Neurosci (2026).

The research offers a new laboratory model for studying motor neuron–related disorders such as spinal muscular atrophy and ALS, though it remains developmental work rather than a therapy.

While the lab-derived neurons show promise, further work is needed to determine how well they model human disease or contribute to therapies for motor neuron disorders.

Evolutionary analyses indicate this dual-origin brain pattern spans species such as chickens, zebrafish, and acorn worms, suggesting two neural systems have been spatially united over hundreds of millions of years.

Evidence of the two-origin arrangement appears in chickens, zebrafish, and acorn worms, implying the pattern dates back more than 550 million years.