Kyle Loh of Stanford University said two separate brain systems research shows the human brain develops from two distinct progenitor cell lineages, with the forebrain and midbrain arising from one type and the hindbrain from another. He said the finding points to an old arrangement that helped shape how the brain is built.
"Our research suggests that evolution took two existing neural systems and pushed them together spatially" Loh said. "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" He also said, "It was actually a summer student’s failed experiment that got us into this,"
Kyle Loh and Stanford University
In early mouse embryo development, one progenitor cell type expresses OTX2 and turns into neurons in the forebrain and midbrain. Another type expresses GBX2 and becomes neurons in the hindbrain, and the same split showed up in human cells grown in dishes.
The researchers then grew functional human hindbrain motor neurons in a dish for the first time by starting with the correct progenitor cell type. That result matters for work on ALS and spinal muscular atrophy, which can cause speech and swallowing difficulties because they affect the hindbrain.
Human cells and hindbrain tissue
The hindbrain coordinates breathing, sleeping, eating and the beating of the heart, while the forebrain is the centre of higher-level thought. Loh said, "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."
The team also studied early-stage embryos of chicken, zebrafish and acorn worms, and found the same two-source pattern in their nervous systems. That supports the idea that the shared two-origin system may have arisen at least 550 million years ago, long before humans diverged from jellyfish, which have two separate nervous systems and split from humans around 600 to 700 million years ago.
OTX2 and GBX2
The practical next step is more work with the hindbrain neurons that are easier to grow once the right progenitor cells are used. Loh’s result gives researchers a clearer way to build human hindbrain tissue in the lab, and that should make it easier to study how GLP-1 drugs such as Ozempic and Wegovy work in people.
The open evolutionary question is how two ancient nervous systems merged into the modern brain, but the developmental map now points to two separate starting lines rather than one shared origin.
