Stanford's Loh lab traces the front and back of the brain to two separate progenitor cells
Kyle Loh's group reports that forebrain and midbrain neurons descend from OTX2 progenitors while hindbrain neurons descend from GBX2 progenitors. Starting from the right cell, they grew human hindbrain motor neurons.
The Scientist · Science desk
What happened
- In mouse embryos, Kyle Loh's Stanford group found that the brain develops from two types of early progenitor cell, proliferative cells with a limited capacity to self-renew.
- One population expresses the gene OTX2 and gives rise to forebrain and midbrain neurons; the other expresses GBX2 and gives rise to hindbrain neurons.
- Experiments on human cells in a dish showed the same division, with hindbrain neurons and forebrain/midbrain neurons coming from different progenitors.
Why it matters
- What's now possible capability ALS and spinal muscular atrophy researchers get a dish source of the cell type those diseases attack, which Loh says should assist work on both.
- What it limits constraint Any protocol that produced hindbrain-like cells from forebrain and midbrain progenitors now needs its cell identity rechecked before results built on it hold.
- Who has to decide decision Groups studying how GLP-1 appetite suppression works have to decide whether to keep inferring from mouse hindbrain or build human GBX2-lineage cells to test it directly.
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The finding came out of a failure. "It was actually a summer student's failed experiment that got us into this," Kyle Loh of Stanford University told New Scientist [6]. Labs trying to grow hindbrain neurons had typically started from progenitor cells destined to become forebrain and midbrain neurons, and, according to Loh, that does not work [7]. Starting from the GBX2 population instead, his group grew functional human hindbrain motor neurons in a dish, which the report describes as a first [8].
That matters for two diseases. ALS is the most common motor neuron disease, and both ALS and spinal muscular atrophy cause speech and swallowing difficulties because they affect the hindbrain [10]. Loh said the easier route to hindbrain neurons should assist research into both [11]. The mouse work was done in embryos, the human work in culture [1][5]. New Scientist's report does not name the journal or give the number of embryos staged.
The evolutionary claim rests on a different kind of evidence. Chicken, zebrafish and acorn worm embryos showed the same two-progenitor pattern [12], and on that basis the researchers suggest the two-origin arrangement is at least 550 million years old [13]. Jellyfish, which have two separate nervous systems, diverged from our lineage 600 to 700 million years ago [15]. Subtract one figure from the other and any merger has to sit between 550 and 700 million years ago, a bracket as much as 150 million years wide [16].
"Our research suggests that evolution took two existing neural systems and pushed them together spatially," Loh said [3]. He put the design cost plainly: "Having the brain as one organ would probably be more efficient, but we rely on this primordial way to make the brain as two separate pieces" [4]. On what the split may have bought, with the hindbrain handling breathing, sleeping, eating and the beating of the heart [9], he said "evolution could play around with the forebrain, and make mistakes and give rise to all the fancy things like memory and creativity" [14]. Those are hypotheses about selection, and what the experiments measured was progenitor identity.
The other use Loh named is pharmacological. GLP-1 drugs including Ozempic and Wegovy suppress appetite in mice by acting on the hindbrain [19], and Loh said human hindbrain neurons in a dish should let researchers investigate how those drugs work in people [11]. The cell type his group reports making is the motor neuron [8], which is what ALS and spinal muscular atrophy attack [10]; the appetite question would need other hindbrain neurons grown from the same GBX2 lineage.
What to watch
- Whether other labs reproduce functional human hindbrain motor neurons starting from GBX2-positive progenitors.
- The publication itself: the journal, the number of embryos staged, and how the motor neurons were assayed as functional.
- Whether the two-progenitor split turns up in lineages beyond mouse, human, chicken, zebrafish and acorn worm, which is what would firm up the 550-million-year floor.
Clarity's read
What the record supports and how the coverage leans. The claims behind it follow.
Reality
- Evidence62
- Adoption
- Not scored
- Hype gap+35
- Incentives50
- Confidence60
Perspective Coverage
6 publishers- Builder
- Builder 38%
- Operator
- Operator 44%
- Investor
- Investor 18%
Claim ledger
Ranked by verification strength, evidence, and original report placement.
- [1]
Loh and colleagues studied early stages of mouse embryo development and found the brain develops from two types of early progenitor cells, proliferative cells with a limited capacity of self-renewal.
- [2]
One progenitor type expresses a gene called OTX2 and turns into the neurons of the forebrain and midbrain; the other expresses GBX2 and becomes the neurons of the hindbrain.
- [3]
"Our research suggests that evolution took two existing neural systems and pushed them together spatially," says Kyle Loh at Stanford University.
- [4]
"Having the brain as one organ would probably be more efficient, but we rely on this primordial way to make the brain as two separate pieces," says Loh.
- [5]
In experiments using human cells in a dish, the researchers found that hindbrain neurons and forebrain/midbrain neurons also develop from different progenitor cells.
- [6]
"It was actually a summer student's failed experiment that got us into this," says Loh.
- [7]
Researchers have typically tried making hindbrain neurons from the progenitor cells destined to become forebrain and midbrain neurons, which doesn't work, Loh says.
- [8]
Armed with this knowledge, the team grew functional human hindbrain motor neurons in a dish for the first time by starting with the correct type of progenitor cell.
- [9]
The hindbrain coordinates fundamental life-sustaining processes such as breathing, sleeping, eating and the beating of the heart, while the forebrain is the centre of higher-level thought.
- [10]
Amyotrophic lateral sclerosis, the most common type of motor neuron disease, and spinal muscular atrophy cause speech and swallowing difficulties because they affect the hindbrain.
- [11]
Now that it is easier to grow human hindbrain neurons in a dish, it should assist ALS and spinal muscular atrophy research and allow investigation of the precise mechanisms of how GLP-1 drugs work in people, Loh says.
- [12]
The researchers also studied early-stage embryos of chickens, zebrafish and acorn worms and found their nervous systems are similarly derived from two different types of progenitor cells.
- [13]
The comparative results suggest the shared two-origin brain system arose at least 550 million years ago.
- [14]
While the hindbrain took care of basic functions for keeping us alive, "evolution could play around with the forebrain, and make mistakes and give rise to all the fancy things like memory and creativity", Loh says.
- [15]
Jellyfish, which our lineage diverged from around 600 to 700 million years ago, have two separate nervous systems.
- [16]
The two source figures place any merger of the two nervous systems between 550 and 700 million years ago, a bracket up to 150 million years wide.
- [17]
The front and back brain regions in people and several other species develop from two distinct cell types in embryos, instead of sharing the same developmental origin as previously thought.
- [18]
"We've shown for the first time that the front of the brain arises from a totally different progenitor cell than the back of the brain," says Loh.
- [19]
Scientists recently discovered that GLP-1 drugs such as Ozempic and Wegovy suppress appetite in mice by acting on the hindbrain.
Sources
5 independent publishers whose own reporting we read for this story.
- discovermagazine.comThe Brain May Be Two Organs, a Discovery That Could Advance ALS Research
1 article · September 18, 2026
- genengnews.comTwo-Organ View of the Human Brain Emerges
1 article · September 18, 2026
- nature.comHow to make a brain: new experiments challenge existing picture
1 article · September 17, 2026
- neurosciencenews.comThe Brain Is Two Separate Organs Joined by Evolution
1 article · September 18, 2026
- newscientist.comOur brain evolved from two primitive nervous systems that merged
1 article · September 18, 2026
- sciencedaily.comStanford scientists discover the human brain may actually be two separate organs
1 article · September 21, 2026
Topics and entities
Topics
- Developmental neurobiology
- Stem-cell-derived neurons
- Motor neuron disease research
- Nervous system evolution
Entities
- Spinal muscular atrophy
- Amyotrophic lateral sclerosis
- Nature Neuroscience
- Stanford Medicine
- Saccoglossus kowalevskii