Study suggests brain forms from two distinct cell lineages
Research published in Nature Neuroscience indicates that the forebrain and hindbrain develop from separate cell populations, a finding that could improve disease modeling and shed light on vertebrate brain evolution.
A new study challenges the traditional view that the brain originates from a single developmental source. Researchers at Stanford University found that the front and back parts of the brain arise from two distinct groups of embryonic cells that later merge, creating the appearance of a single organ.
The team examined mouse embryos during gastrulation and identified one cell population expressing the gene Otx2, linked to forebrain and midbrain development, and another expressing Gbx2, associated with midbrain and hindbrain formation. Chromatin analysis showed each group maintained a unique configuration, supporting 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," said Rayyan Jokhai, a graduate student in the lab.
Using the insights from mouse embryos, the researchers guided human stem cells to become functional hindbrain motor neurons, which are difficult to produce in the laboratory. These neurons generate proteins typical of hindbrain regions that control facial and swallowing muscles, offering a new platform for studying conditions such as spinal muscular atrophy and amyotrophic lateral sclerosis.
"We cannot sample living motor neurons from a patient's hindbrain to watch how these diseases attack these neurons. Growing these hindbrain motor neurons in a dish gives us a way to investigate these diseases," said Kyle Loh, an associate professor of developmental biology.
The findings also have evolutionary implications. Analysis of existing data from macaques, zebrafish, chickens and even acorn worms revealed the same two cell populations, suggesting the modular developmental pattern dates back hundreds of millions of years.
"The developmental separation between the anterior lineage (forebrain/midbrain) and the posterior lineage (hindbrain) is traceably ancient," said Anna Di Cosmo, a biology professor at the University of Naples Federico II.
Loh's team proposes that early vertebrate ancestors may have possessed two separate nervous systems that later fused to form a single brain, though the exact timing and mechanisms remain uncertain.
"It is important to emphasize that this is only an idea, and it might change as scientists learn more," Loh added.