Human brain is 2 organs, not 1, Stanford study reveals

Researchers at Stanford Medicine have made a striking discovery that challenges the long-held understanding of how the human brain develops: it consists of two distinct organs that evolved independently before becoming closely integrated.

The study, published in Nature Neuroscience on September 18, overturns the prevailing theory that a single progenitor cell gives rise to the entire brain during early development. Researchers found that the brain's front and back regions emerge from separate progenitor cells and follow parallel developmental pathways.

The forebrain and midbrain develop from one population of progenitor cells, while the hindbrain develops from another. The hindbrain controls vital automatic functions, including breathing and heartbeat, while the forebrain is responsible for higher-level functions such as language, consciousness and abstract reasoning.

The researchers identified the developmental split by examining early embryonic development and found that the two progenitor populations remain distinct from the earliest stages. They also traced the pattern across more than 550 million years of evolution, finding evidence of the same two-origin arrangement in species including chickens, zebrafish and acorn worms.

The breakthrough could have major implications for research into serious brainstem disorders such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Scientists have struggled to generate human hindbrain neurons in laboratories, limiting research into these diseases.

Using their new understanding, the team successfully produced functional hindbrain motor neurons from human pluripotent stem cells in the laboratory. The achievement could provide a new model for studying how these devastating diseases affect brainstem neurons and potentially aid future treatment research.

The study was led by Kyle M. Loh, with graduate students Carolyn C. Dundes and Rayyan Jokhai serving as co-first authors. Researchers from Caltech and UCSF also contributed.