Researchers at Stanford Medicine have found evidence that the human brain develops from two distinct groups of progenitor cells rather than from a single source. The findings challenge the long-standing view that the entire brain develops from one common population of early cells.
The study found that one progenitor population develops into the forebrain and midbrain, while another forms the hindbrain. The two populations emerge separately during an early stage of embryonic development and remain committed to their respective regions.
Researchers identified different genetic markers in the two cell populations. The forebrain and midbrain progenitor expresses Otx2, while the hindbrain progenitor expresses Gbx2. The researchers found that the two populations have different patterns of gene activity and chromatin organisation from the earliest stages they examined.
The finding also helped the team produce functional human hindbrain motor neurons from pluripotent stem cells in the laboratory. These cells showed electrical activity and characteristics associated with hindbrain neurons involved in controlling facial and swallowing muscles.
The researchers traced the two-origin pattern through more than 550 million years of evolution. Similar developmental pathways were identified in animals including chickens, zebrafish and acorn worms. The findings could improve research into conditions affecting the brain stem, including spinal muscular atrophy and amyotrophic lateral sclerosis.
