STANFORD-LED STUDY FINDS HUMAN BRAIN HAS TWO DISTINCT ORIGINS

A Stanford-led team says the human brain develops from two separate, collaborating neural systems that form in parallel from the earliest stages of embryonic life, according to a study published in Nature Neuroscience. The study found that different brain regions arise from two distinct progenitor cell types, one producing the forebrain and midbrain, the other forming the hindbrain. Researchers identified the split by studying mouse embryos during gastrulation, then confirmed human stem cells follow the same two paths. For what they describe as a first, the team guided human stem cells into functioning hindbrain motor neurons.

According to the study, progenitor cells forming the forebrain and midbrain express a gene called Otx2, while those destined for the hindbrain express a different gene, Gbx2. Both cell types build the finished brain, the researchers said, but their roles are not interchangeable and their DNA is packaged differently, each with a distinct chromatin structure. Developmental biologist Rayyan Jokhai, co-first author with Carolyn Dundes, said stem cell biology has traditionally focused on producing a final cell type rather than the earliest stages of embryonic development. Jokhai said close attention to that early stage allowed the team to identify the split.

The researchers said the different chromatin structures could explain why past laboratory attempts to grow hindbrain cells have often failed, since scientists may have used progenitor cells fated to become forebrain tissue. They said the findings suggest neural progenitor cells should not be treated as interchangeable. The study draws on evidence from both mouse embryos and human stem cells. The generation of functioning hindbrain motor neurons from human stem cells, described as a first, points to a new approach for laboratory research into brain development.