Stanford researchers found that the forebrain and midbrain arise from Otx2-expressing progenitors, while the hindbrain comes from a separate Gbx2 lineage. The finding could improve lab models of ALS and spinal muscular atrophy, but does not demonstrate a treatment.
The cell populations did not overlap at the earliest developmental stages examined. Researchers also found differences in chromatin—the material that packages DNA and affects which genes are accessible—which they said help explain why one population does not readily convert into the other. The same two-origin pattern appeared in chickens, zebrafish and acorn worms, suggesting it is evolutionarily conserved.
The study suggests that efforts to grow hindbrain neurons from stem cells directed toward forebrain or midbrain identities start from a different developmental lineage. Lab-grown hindbrain neurons could help researchers study disease mechanisms and candidate treatments, but moving toward clinical use would depend on producing them at scale and accurately reproducing human disease features.
