Stanford Medicine researchers published a study in Nature Neuroscience on September 18, revealing that the human brain consists of two ancient nervous systems derived from completely separate starter cells that never mix during embryonic development.
Embryonic Development Reveals Two Neural Lineages
To understand the structural origins of the brain, researchers examined mouse embryos during gastrulation, the early developmental stage when the body first takes shape. During this process, cells that start as pluripotent—capable of becoming any cell type—narrow their flexibility within days.
The anterior neural ectoderm cells, characterized by the active gene Otx2, give rise exclusively to the forebrain and midbrain. Meanwhile, posterior neural ectoderm cells build the hindbrain, which controls automatic life functions like breathing, heartbeat, and swallowing. Lead authors Rayyan Jokhai and Carolyn Dundes found that these two construction crews never mix their cells, splitting into two separate groups assigned to the forebrain and hindbrain.
Chromatin Packaging Sets Cell Identity Early
This architectural split explains why earlier attempts by scientists to convert forebrain starter cells into hindbrain cells in the lab consistently failed.
By working with human pluripotent stem cells and guiding them specifically down the posterior pathway, the Stanford team successfully grew hindbrain neurons in the lab.
Evolutionary Conservation Across Species
The dual-origin nervous system plan is not unique to mammals. The research team discovered the same developmental split in chickens, zebrafish, macaques, and acorn worms—marine creatures that share a common ancestor with humans dating back more than 550 million years.
Senior author Kyle Loh said the findings are important for laboratory research. Our discovery means that we can now grow neurons from the back of the brain, the hindbrain, in a petri dish and study their functions.
Evolutionary Origins
These two systems developed from separate starter cells and retain separate identities at the deepest level, though they are experienced as a single organ.
Implications for Neurodegenerative Disease Research
The ability to generate hindbrain motor neurons in a laboratory setting offers new pathways for studying neurodegenerative conditions. ALS is often diagnosed in people between the ages of 40 and 70 and affects both the hindbrain and forebrain.
Because these vulnerable motor neurons descend from the posterior lineage, researchers now have a reliable cellular model to investigate disease mechanisms and test potential regenerative therapies. This discovery may help explain why scientists struggled for decades to grow certain brain cells in the lab.
Frequently Asked Questions About the Two-Part Brain Discovery
What triggers the separation of the forebrain and hindbrain starter cells?
The separation occurs during gastrulation, an early embryonic stage, governed by chromatin packaging that determines which genes a cell is able to switch on.
Can forebrain starter cells be converted into hindbrain cells?
No. According to the researchers, these cells are fundamentally incapable of becoming the other type because their genetic “recipes” are locked or open based on their specific lineage.
How does this discovery impact ALS and SMA research?
By identifying the distinct posterior origin of hindbrain motor neurons, scientists can now grow these specific cells in the lab to study diseases like amyotrophic lateral sclerosis and spinal muscular atrophy.
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