Lab-Grown Brain Models Gain a Sense of Place

“By introducing regional identity into these models, we can begin asking questions about development and disease that were difficult to address with conventional organoids,” says lead author Momoko Watanabe (left), UC Irvine assistant professor of anatomy and neurobiology and a faculty member of the Sue & Bill Gross Stem Cell Research Center, here with study co-author Yuan-Chen Tsai, PhD, a postdoctoral research fellow in the Department of Anatomy & Neurobiology. 

The human brain is often described as one of the most complex structures in biology, and much of its power comes from how it’s organized. Its outer layer, the cerebral cortex, is not one uniform sheet. As the brain develops, it divides into distinct areas that each take on different jobs, from movement and vision to memory, language and social understanding.

Scientists call this process “arealization,” and they believe it underpins much of what the brain can do. It may also help explain what goes wrong in some conditions that affect brain development.

That organization draws interest well beyond neuroscience. Engineers have long borrowed ideas from the brain – which builds itself without a blueprint and runs on very little power – for work in computing and robotics. But the biology has been hard to study because most of this patterning happens before birth.

Even early in development, the human brain has a sense of place. Chemical signals help tell developing cells where they are, contributing to differences between areas at the front and the back of the cerebral cortex.

Until now, scientists have had difficulty reproducing that organization in lab-grown models of the human brain.

Researchers at the University of California, Irvine have developed a new approach that lets them engineer lab-grown human brain tissue with a defined regional identity, producing organoids with characteristics of either the front or the back of the developing cerebral cortex. The advance could help scientists better understand how the human brain develops and what happens when that process is disrupted in neurodevelopmental disorders.

In a study published Aug. 20 in Cell Stem Cell, the UC Irvine-led team created human neocortical organoids – small, three-dimensional tissues grown from human stem cells that copy important features of the developing cerebral cortex. Each organoid was steered to take on the identity of either a front or a back region.

“Brain organoids have become powerful tools for studying human development, but the human brain is a highly organized space,” says lead author Momoko Watanabe, PhD, assistant professor of anatomy and neurobiology in the UC Irvine School of Medicine and a faculty member of the Sue & Bill Gross Stem Cell Research Center. “By introducing regional identity into these models, we can begin asking questions about development and disease that were difficult to address with conventional organoids.”

Read the full feature article in UC Irvine News.