"The brain appears as one organ," said study co-author Kyle Loh, an associate professor of developmental biology at Stanford University. "However, we discovered that the front part of the brain and the back part of the brain come from different sources, which are pushed together to create the appearance of a single organ," Loh told Live Science in an email.
The human brain is divided into three main regions — called the forebrain, midbrain and hindbrain — that perform different but interconnected functions.
Historically, the hindbrain has been difficult to study. One reason is that scientists have faced persistent challenges in generating functional hindbrain neurons in laboratory conditions.
One cell population expressed a gene called Otx2, which helps to direct the early development of the forebrain and midbrain. The second group of cells expressed the gene Gbx2, which is involved in the development of the midbrain and hindbrain.
This photograph shows a 9.5-day-old mouse embryo and depicts the two separate developmental origins of the brain. The forebrain and part of the midbrain (blue) express the Otx2 gene, while the hindbrain and the rest of the midbrain (red) express Gbx2. The red cell population also extends into the spinal cord. (Image credit: Stanford Medicine)The team also examined chromatin, the molecular structure that packages DNA tightly inside the nucleus and helps regulate which genes a cell can use. The two cell populations show different chromatin configurations, the team found, which further supports the idea that they follow separate developmental pathways.
"Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible," study co-author Rayyan Jokhai, a graduate student in Loh's lab, said in a statement.
Why it matters
In several neurological diseases, including spinal muscular atrophy and amyotrophic lateral sclerosis, motor neurons deteriorate and affected patients can lose their ability to swallow, speak and breathe independently.
The new findings could also reveal something fundamental about the evolution of vertebrate animals.
And even in acorn worms — a marine invertebrate whose evolution diverged from vertebrates about 550 million years ago — they again found these two distinct groups of cells.
Related stories"The Stanford discovery establishes that the deep ancestry of the vertebrate brain is fundamentally modular," said Anna Di Cosmo, a professor of biology at the University of Naples Federico II in Italy who wasn't involved with the study. "The developmental separation between the anterior lineage (forebrain/midbrain) and the posterior lineage (hindbrain) is traceably ancient," Cosmo told Live Science in an email.
However, the study doesn't reveal exactly when the two pathways arose or establish how they integrated. "It is important to emphasize that this is only an idea, and it might change as scientists learn more," Loh said.
See how much you know about the most complex organ in the human body with our brain quiz!
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