Human brain is two separate organs

Researchers have shown that what is commonly called the brain is actually two separately originated organs packaged together: an anterior system (forebrain and midbrain) and a posterior hindbrain/brainstem. During gastrulation they identified two mutually exclusive progenitor populations - one marked by Otx2 that produces fore- and midbrain, and one marked by Gbx2 that produces hindbrain - with distinct chromatin states that lock each lineage into its fate. The pattern appears conserved across species from zebrafish and chickens to acorn worms and mirrors ancient dual nervous systems, overturning the long-held idea of a single common progenitor for the entire brain.

Using that developmental insight, human pluripotent stem cells were directed for the first time into authentic hindbrain motor neurons that fire action potentials and express proteins identifying hindbrain segments controlling face, swallowing and breathing. This resolves why past efforts failed when they attempted to convert forebrain progenitors into hindbrain cells. The advance enables laboratory models of brainstem disorders such as spinal muscular atrophy and ALS, which impair swallowing and respiration, and opens paths to study hindbrain circuits involved in hunger and potential regenerative therapies. The work, led by Kyle Loh and published in Nature Neuroscience, provides a new framework for studying brain development, disease modeling and evolution.