Back to the beginning

Alex Eben Meyer

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Studying the billions of specialized cells in the human brain helps scientists understand disorders such as microcephaly, schizophrenia, and autism. But by the time a scientist can slice into an adult brain, it’s usually too late to identify the molecular roots of their disease. 

To Nicola Micali, an associate research scientist at the Yale School of Medicine, the answer may lie in the humble origins of the brain: stem cells. “By studying neural stem cells, we can identify mechanisms that are important to our understanding of brain disorders,” he says.

Stem cells play crucial roles during the development of the brain, but this is nearly impossible to study in humans. Instead, Micali mimicked this process in a lab dish. He used molecular signals to turn skin cells into stem cells and then control their differentiation into brain cells and structures. By collecting molecular data from the cells throughout this process, Micali found that many of the genes involved in brain disorders were active during early stages of development. His team shared their results in a study published in Nature Communications.

“It is possible that these genes are altering the patterning of the brain in very early phases of brain development,” thus interfering with the formation of critical brain structures, Micali said. Other scientists had speculated that brain disorders arose due to changes before birth, but they hadn’t been able to study these earliest days of development with traditional methods. “That’s the beauty of modeling brain development in vitro,” Micali says.

To trace these diseases back one step further, Micali’s team identified molecules that might control these genes’ activity in neural stem cells. Some of these molecules seemed to be involved in multiple brain disorders, and through computational simulations, they showed that interfering with these upstream molecules might change how brain cells develop.

Micali believes the study could help scientists better understand how these diseases develop and why they emerge in certain people. “The origins of these diseases must be even earlier than we thought,” he says.