Overview
- Stanford-led researchers reported in Nature Neuroscience on Sept. 18, 2026, that the forebrain and midbrain arise from Otx2-expressing progenitors while the hindbrain derives from a separate Gbx2-expressing progenitor population that do not overlap.
- Epigenomic analysis found the anterior and posterior neural ectoderm have different chromatin configurations at gastrulation, which lock each progenitor onto its fate and explain why converting one lineage into the other has repeatedly failed.
- Using those developmental signals, the team guided human pluripotent stem cells to become electrically active hindbrain motor neurons that express markers for segments controlling facial movement and swallowing.
- The advance creates an experimental platform to study brainstem disorders such as spinal muscular atrophy and ALS and to test drugs on human hindbrain circuits, though the authors note they cannot fully exclude a very brief, previously missed common progenitor and plan follow-up mapping of spinal cord origins.
- Comparative evidence from chicken, zebrafish and acorn worms suggests the dual-origin pattern is evolutionarily conserved over roughly 550 million years, and the work was conducted with collaborators at Caltech and UCSF and supported by multiple funders including the NIH.