Stanford scientists report that the human brain originates from two separate developmental systems, enabling the first lab‑grown hindbrain neurons and new avenues for ALS and SMA research.
Stanford Medicine researchers have shown that the human brain is built from two distinct cellular systems that evolved separately. One progenitor population expressing Otx2 gives rise to the forebrain and midbrain, while a second population expressing Gbx2 forms the hindbrain. Chromatin analyses indicate these lineages remain separate from the earliest gastrulation stages.
Using this insight, the team guided human pluripotent stem cells to become functional hindbrain motor neurons that fire action potentials and express region‑specific proteins. This marks the first successful generation of human hindbrain neurons in vitro.
The findings suggest an evolutionary fusion of two ancient nervous systems and provide a model for studying brain‑stem diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis, where hindbrain neurons are affected. Researchers plan to explore how the spinal cord develops and how these diseases disrupt hindbrain cells.
Further work is needed to clarify the developmental relationship of the spinal cord to the two brain origins and to translate the new cell‑culture system into therapeutic strategies.