HMN 2026: How Organs help shape the nervous systems that control them

A new Yale study reveals that major organ systems in the body aren’t just passive structures operating on directions from command central—the brain—but instead are active participants in controlling their own functions.

Writing in the journal Nature, a team of researchers led by Yale’s Rui Chang demonstrates how organs develop and maintain their own neural circuitry, which in turn communicates with the brain in a sort of two-way conversation.

The findings provide a new understanding of how the body and brain communicate via networks of neurons embedded inside organs that constitute a mini-nervous system, called “organ intrinsic nervous systems,” which help control critical functions such as digestion, heart rhythm, breathing, insulin secretion, and immune responses, the researchers say.

They also suggest that problems in these mini, organ-based nervous systems may contribute to diseases such as Parkinson’s disease, autonomic disorders, and inflammatory illnesses.

“This study helps us understand how different organs build their own nervous systems to facilitate communication with the brain,” said Chang, associate professor of neuroscience and of cellular and molecular physiology at Yale School of Medicine (YSM) and lead author of the study.

“To perform a specific function, an organ needs to have its own anatomical basis and its own molecular basis. This study describes how the organ shapes its own nervous system to achieve that goal.”

Working with neurons from the heart, lungs, pancreas, and intestines, researchers found that these organs actively help build and shape their own internal nervous systems early in development. And although these budding neurons arrive with a basic blueprint, they are not on autopilot. The organs themselves help determine how neurons progress and organize themselves into systems.

“These individual nervous systems are physically located on the organs we studied, which was the big breakthrough,” said co-senior author Le Zhang, assistant professor of neurology and of neuroscience at YSM. “The key was the technology that we now have, which for the first time let us detect these systems at such high resolution.”

In their work, researchers used advanced imaging, genetic sequencing technologies, and mouse models to study developing nervous systems in multiple organs. One key discovery was that nerve cells in different organs organize themselves differently depending on their migration during embryonic development. Neurons in the intestine and pancreas, for example, spread widely throughout the organ, while heart and lung neurons stay clustered in tight groups.

The surrounding environment inside an organ also played a major role in development and had the ability to change the identity of neurons, they found. Heart tissue, for example, could reprogram gut neurons so they behaved more like heart neurons.

“While for now this remains far from any clinical application, one of the really exciting potential applications of these findings is that our study shows that you can potentially convert the cells from one organ to the cells in different organs,” Chang said. “Imagine what that could mean for patients dealing with organ-based disease.”

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