Researchers at Stanford University School of Medicine have revealed that the human brain originated from two different nervous systems that evolved independently over hundreds of millions of years.
The study, published in the journal Nature Neuroscience, indicates that the brain does not descend entirely from a single set of progenitor cells during the early stages of embryonic development, as was previously thought, but is formed from two separate developmental pathways that later converge.
The brain comprises three main regions: the forebrain, the midbrain, and the hindbrain. The forebrain is associated with functions such as language, consciousness, and thought, while the hindbrain handles essential functions, including breathing, regulating heartbeat, sleep, and appetite. It also controls the facial muscles, tongue, and larynx responsible for speech and swallowing.
The researchers arrived at these findings by studying the early stages of mouse embryo development, where they discovered two different sets of progenitor cells.
The study showed that one group carries a gene known as Otx2 and is directed towards the formation of the forebrain and midbrain, while the other group carries a gene known as Gbx2 and is directed towards the formation of the hindbrain.
The two groups remained separate from the earliest stages of development, and researchers also found clear differences in chromatin, the structure that regulates gene activity within the cell. These findings suggest that the fate of each cell group is determined very early in embryonic development.
Kyle Loh, an associate professor of evolutionary biology, said the researchers have shown for the first time that the front part of the brain originates from progenitor cells that are completely different from those from which the back part originates.
This discovery helped researchers understand why it is difficult to produce hindbrain neurons in the lab. After identifying the correct developmental pathway, the team was able to guide human pluripotent stem cells to become functional motor neurons belonging to the hindbrain.
These cells exhibited electrical activity and properties similar to normal cells, including the production of proteins associated with areas responsible for controlling facial muscles and swallowing.
Researchers believe this ability could help in studying diseases that affect the brainstem, such as spinal muscular atrophy and amyotrophic lateral sclerosis, which damage important nerve cells and may cause loss of the ability to swallow and breathe.
The research wasn't limited to mice and human cells; scientists found a similar pattern in chickens, zebrafish, and acorn worms—organisms that share a distant evolutionary ancestor with humans. They also noted that jellyfish possess two separate nervous systems, even though their evolutionary lineage diverged from the lineage that led to humans approximately 600 to 700 million years ago.
Loh said the results suggest that evolution may have combined two nervous systems that existed separately, to later function as one system.
Researchers hope to expand their studies to understand the evolutionary origin of the spinal cord, and to study how brain cells in the hindbrain are affected by diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis, which may help in the future to develop new treatments.
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