Stanford research suggests human brain might be two organs fused together

While researchers at the prestigious US university of Stanford were trying to find a method to study a part of the brain that is difficult to access in living patients, an unexpected finding now suggests that the brain is not one whole organ that develops throughout the same timeline, as was widely assumed until now.

The human hindbrain, located at the back of the brain and responsible for vital functions such as breathing and swallowing, has long been difficult to study in laboratory settings, as an article published by the institution on this finding recalls.

For decades, scientists have struggled to grow its neurons, limiting their ability to investigate diseases that progressively impair these functions.

Researchers at Stanford's medical school have now successfully grown functional human hindbrain motor neurons — nerve cells responsible for controlling muscles — after identifying a developmental divergence that occurs as an embryo begins to form. Their findings indicate that producing these cells requires a different developmental starting point from the one that gives rise to other major regions of the brain.

For decades, scientists had generally believed that a single type of progenitor, or precursor, cell produced the entire brain. According to that model, the three major regions of the adult brain — the forebrain, midbrain and hindbrain — all originated from the same developmental source.

The regions eventually develop distinct functions. The forebrain is involved in language, consciousness and abstract reasoning, including abilities such as mathematics and poetry. The hindbrain, meanwhile, regulates automatic processes including heartbeat, breathing, sleep and hunger. Its neurons also control muscles in the face, tongue and throat that are essential for speech and swallowing.

“We’ve shown for the first time that the front of the brain arises from a totally different progenitor cell than the back of the brain,” said Kyle Loh, PhD, an associate professor of developmental biology and the study’s senior author. “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.”

The researchers started with human pluripotent stem cells, which have the ability to develop into any cell type in the body, and directed them through the newly identified developmental pathway.

The resulting neurons were capable of producing action potentials, the electrical signals nerve cells use to communicate. They also generated proteins associated with hindbrain regions that control the muscles involved in facial movement and swallowing.

The ability to produce these cells could provide researchers with a new way to study spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.

Brainstem tissue cannot be collected from living patients, while the longstanding difficulty of growing human hindbrain neurons has significantly restricted research into how these diseases affect the cells.

SMA is a major genetic cause of death among children under the age of 1. ALS, which is often diagnosed between the ages of 40 and 70, affects both the hindbrain and forebrain, the part of the brain involved in higher-level thinking.

In both conditions, certain hindbrain neurons progressively lose their function. As the diseases advance, patients can lose the ability to swallow, allowing food or liquid to enter the lungs and potentially cause pneumonia. Eventually, they can also lose the ability to breathe.

“Now we have a model to better understand these devastating diseases, and work toward regenerative therapies for them,” said Rayyan Jokhai, a Stanford graduate student and co-first author of the study. “This is a very exciting new frontier in brain research.”

By Nazrin Sadigova