Human brain is two separate organs, Stanford Medicine-led research finds

A groundbreaking Stanford Medicine-led study has revealed that the human brain is comprised of two distinct organs that evolved independently over millions of years. This finding challenges the long-held belief that the brain is a single, unified organ. Dr. Kyle Loh, an associate professor of developmental biology, stated that the front of the brain - responsible for higher-level thinking - emerges from a different progenitor cell than the back of the brain, which controls essential automatic functions such as breathing and heartbeat.

The discovery could aid research into devastating neurological diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis, which affect the hindbrain. For decades, scientists have struggled to produce hindbrain neurons in the laboratory, hindering progress in treating these diseases. However, the researchers' breakthrough came from studying the earliest moments of embryonic development, during a stage called gastrulation.

By examining developing mouse embryos, the researchers identified two different brain progenitor cells with separate developmental paths. One cell population, expressing a gene called Otx2, gives rise to the forebrain and midbrain, while the other, expressing a gene called Gbx2, forms the hindbrain. These two cell populations never overlap, solidifying their respective fates from the earliest stages of development.

The researchers also discovered that the chromatin configuration, which determines gene accessibility, differs between the anterior neural ectoderm (future forebrain and midbrain) and the posterior neural ectoderm (future hindbrain). This chromatin difference essentially locks each progenitor cell into its respective fate, like travelers on parallel tracks that never cross.

With this newfound knowledge, the team successfully coaxed human pluripotent stem cells to become functional hindbrain motor neurons in the laboratory. These lab-grown neurons displayed all the hallmarks of authentic hindbrain cells, including electrical activity and proteins specific to segments controlling facial and swallowing muscles.

Furthermore, the study found that this two-origin brain pattern exists in chickens, zebrafish, and acorn worms, a distant common ancestor of humans, dating back over 550 million years. This shared evolutionary history suggests that the two-brain neuron system is a fundamental aspect of vertebrate development.

The implications of this discovery are far-reaching, providing new avenues for understanding and treating diseases that affect the brain stem. By focusing on the earliest stages of embryonic development, researchers can now explore the fundamental differences between the two brain regions, potentially leading to groundbreaking treatments for conditions like spinal muscular atrophy and amyotrophic lateral sclerosis.