Human Brain Composed of Two Separate Organs, New Study Reveals

A recent study by Stanford University scientists has determined that the human brain is not a single organ, but rather two distinct entities that develop separately. This revelation, published in the journal Nature, could significantly alter research approaches for severe diseases affecting the brain stem.

Historically, the brain has been understood as having three primary regions: the forebrain, responsible for higher-level cognitive functions such as language and abstract thought; the midbrain, which handles sensory processing and motor control; and the hindbrain, often referred to as the brain stem, which regulates essential life functions like breathing, heart rate, and swallowing.

The new research indicates that the forebrain and midbrain develop from one type of progenitor cell, characterized by the gene Otx2, while the hindbrain develops from a separate progenitor cell expressing the gene Gbx2. These two cell types do not intermingle during the earliest stages of embryonic development, suggesting distinct developmental pathways.

This finding addresses a long-standing challenge in researching conditions like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), both of which involve the progressive degeneration of hindbrain neurons. For decades, scientists have struggled to cultivate hindbrain neurons in laboratory settings, largely due to the assumption that all brain regions originated from the same developmental source.

"Our discovery means that we can now grow neurons from the back of the brain, the hindbrain, in a Petri dish and study their functions," stated Kyle Loh, senior author of the study and associate professor of developmental biology. "Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible."

By understanding these separate developmental origins, researchers have successfully grown functional hindbrain motor neurons in the lab for the first time. These lab-grown neurons exhibit key characteristics of native hindbrain cells, offering a new model to investigate potential treatments for diseases that impact the brain stem. This breakthrough opens new avenues for understanding the mechanisms behind these debilitating conditions and developing regenerative therapies.

The study also traced this dual-origin brain pattern through evolutionary history, finding similar arrangements in species like chickens, zebrafish, acorn worms, and jellyfish, suggesting the origins of these distinct neural systems date back over 550 million years. "I was surprised at our findings because the word ‘brain’ implies a contiguous organ that likely has a singular origin," commented graduate student Rayyan Jokhai. "But even 500 million years ago, there were these separate neural systems, which now almost operate as one."