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

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A new study led by Stanford Medicine found the brain is two separate organs adjacent to one another. The finding could aid research into devastating neurological diseases.

For centuries, scientists have thought of the brain as a single, unified organ. But new research led by Stanford Medicine reveals that what we call the brain is two distinct organs that evolved independently over hundreds of millions of years.

The discovery overturns a prevailing model of brain development. For decades researchers have subscribed to the theory that there is a single progenitor cell early in development that gives rise to the entire brain. This model suggested all parts of the brain shared a common developmental origin.

In-Depth Developments & Factual Context

The new research finding shows that the human brain consists of two ancient nervous systems cleverly packaged together - a more primitive part that regulates our hearts' beating, our breathing and other functions, and another that makes us distinctly human, capable of poetry, mathematics and wondering about our own origins.

The discovery could help explain why scientists have struggled for decades to grow certain types of brain cells in the laboratory - and it opens new avenues for studying devastating diseases that affect the brain stem, such as spinal muscular atrophy (also known as SMA) and amyotrophic lateral sclerosis (also known as ALS or Lou Gehrig's disease).

"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, associate professor of developmental biology. "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."

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The findings were published in Nature Neuroscience Sept. 18. Loh is the senior author. Graduate students Carolyn Dundes and Rayyan Jokhai are co-first authors of the research.

The adult brain has three main regions: the forebrain, midbrain and hindbrain. The forebrain handles higher-level thinking - language, consciousness and abstract reasoning. In contrast, the hindbrain, located at the back of the skull and often called the brain stem, controls essential, automatic functions that keep us alive: breathing, sleeping, and regulating our heartbeat and hunger urges. The hindbrain neurons also control the muscles of the face, tongue and throat, which affect speech and swallowing.

Despite the critical importance of the hindbrain, scientists have struggled for decades to generate human hindbrain neurons in the laboratory. This gap has hampered research into devastating diseases affecting the brain stem, including spinal muscular atrophy and amyotrophic lateral sclerosis.

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SMA is a leading genetic cause of death in children under 1 year of age. ALS, which is often diagnosed between the ages of 40 and 70, affects both the forebrain and the hindbrain. In both disorders, certain hindbrain neurons gradually cease to function, and the patient loses the ability to swallow, which can cause pneumonia when food or liquid is inhaled into the lungs; eventually, patients lose the ability to breathe.

The researchers' breakthrough came from studying the earliest moments of embryonic development, during a stage called gastrulation when the body first takes shape. Jokhai and Dundes discovered that the hindbrain follows a separate developmental path, running in parallel to - rather than branching off from - the pathway that creates the forebrain and midbrain.

The researchers learned this from examining developing mouse embryos. They identified two different brain progenitor cells. One, which expresses a gene called Otx2, is destined to become the forebrain and midbrain. The other, which expresses a gene called Gbx2, is committed to forming the hindbrain. They showed that these two cell populations never overlap; they are mutually exclusive from the earliest stages of development.

The team then examined the DNA packaging, or chromatin, in these cells. Chromatin is a way cells determine which genes can be easily accessed and which are bundled away out of reach. What they found was striking: The anterior neural ectoderm (future forebrain and midbrain) and posterior neural ectoderm (future hindbrain) have fundamentally different chromatin configurations. These differences essentially locked each progenitor cell into its respective fate, like travelers on parallel tracks that never cross.

"Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible," Jokhai said.

This revelation explained decades of frustration in the field - scientists had been trying to turn one type of progenitor cell into another that it is fundamentally incapable of becoming.

Reporting synthesized and verified under Nexvoro.tech editorial guidelines. Full primary records referenced via Stanford Medicine.