The brain may not be a single organ after all
By
Mike McRaeSeptember 21, 2026
The brain may not be a single organ after all
What looks like a single organ could be two made one.
(u_if8o5n0ioo/pixabay/Canva)
View 1 Image
1
/
1
What looks like a single organ could be two made one.
(u_if8o5n0ioo/pixabay/Canva)
Whileone part of your brainprocesses these words,another partis keeping you alive, regulating your heartbeat, maintaining your breathing, and hopefully ensuring you don’t nod off before you’ve reached the end.
According to a recent investigation on mice by Stanford University researchers, there’s a case for treating these two neural continents as separate organs, each with very distinct embryological – and potentially evolutionary – origins.
The distinction goes far beyond mere semantics. It may finally reveal how to set blank stem cells on a path to becoming either a “thinking” and “sensing” part of the humanforebrainandmidbrain, or a “life-sustaining” piece of the human hindbrain.
“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 developmental biologist Kyle Loh, senior author in the landmark new study. “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.”
Roughly three weeks after conception, your body consisted of a few tens of thousands of cellsdivided intothree distinct layers.
One would give riseto the tissues of your gut, lungs, bladder, and other internal organs, like your liver and pancreas.A second layerwas destined to develop your reproductive organs, skeleton, muscles, and circulatory system.
A third layer of cells, called theectoderm, would transform into the skin and nervous system.
One big question has always been whether cells in the ectoderm were already destined to become the forebrain, midbrain, and hindbrain.
As far back as the 1950s, the Dutch embryologistPeter Nieuwkoopargued that the human brain’s precursor cells were all identical in the ectoderm. The brain itself is structured in a seamless fashion that makes this seem likely as well.
Yet numerous animal studies have suggested otherwise, leaving the debate wide open.
A key challenge is distinguishing a cell’s intrinsic fate from a destiny imposed externally by its relative position. There’s no easy way to jumble cells in an ectoderm and see if they still make a functioning brain.
Using mice as their animal of choice, Loh and his team followed the threads of genetic expression through critical moments of change in the neural ectoderm in a week-old mouse embryo, using staining and RNA sequencing to distinguish two mutually exclusive populations of cells described asSox2+ Otx2+(aNE) andSox2+ Gbx2+(pNE).
“The locations of aNE and pNE in the E7.5 mouse embryo generally comport with the positions of cells fated to, respectively, generate future forebrain/midbrain versus hindbrain in classical fate maps,” the team writes in their published report.
This implies that our own hindbrain is already represented by an exclusive lineage of cells distinct from the forebrain and midbrain just three weeks after conception, roughly when other major organs like the heart are distinguishing themselves.
Looking closer, Loh and his team uncovered cytological differences in how chromosomal material was packaged in each cell type, further demonstrating key differences that separated each population of future brain tissues.
The discovery explains why attempts in the past to develop hindbrain neurons from ectoderm stem cells failed – those cells had already been locked in as forebrain or midbrain neurons.
“In stem cell biology, people are always fixated with creating the end cell type, like the neuron,” says Rayyan Jokhai, a co-first author on the study. “But it’s important to begin at the earliest stages of embryonic development. Our careful attention to that early time point allowed us to find this fundamental split in brain development.”
With this in mind, the team successfully coaxed an embryonic stem cell into becoming a motor neuron that wouldn’t be out of place in our own hindbrain, opening the way to creating laboratory models of brain tissue that can be used to study or even one day treatmotor neuron diseasessuch asamyotrophic lateral sclerosis.
The early distinction in brains could be a legacy of our deep evolutionary past. Using existing studies to compare aNE and pNE populations in the embryos of other vertebrates, such as macaques and zebrafish, and invertebrates such asacorn worms, the team found the same patterns being conserved, suggesting animals have been raising two different brains for hundreds of millions of years.
“I was surprised at our findings because the word ‘brain’ implies a contiguous organ that likely has a singular origin,” says Jokhai alongside Carolyn Dundes. “But even 500 million years ago, there were these separate neural systems, which now almost operate as one, which is very cool.”
This research was published inNature Neuroscience.
Source:Stanford Medicine
