Grant: Joint Canada-Israel Health Research Program

The cerebral cortex is the region of the brain that allows us to sense the environment by sight, sound, touch, and smell, and to respond to it by movement or communication. The cerebral cortex also allows us to experience complex human emotions such as love, empathy, fear, and sadness. To perform these complex functions, this region of the brain is compartmentalized into primary sensory areas that are responsible for the senses of touch, hearing, and vision, and a primary motor area that controls movement. This partitioning is essential for normal functioning, and defects in regionalization may underlie certain diseases, such as autism spectrum disorder (ASD). The biggest challenge in studying neuropsychiatric disorders is that they often have their root causes in early embryonic development, making it near impossible to visualize the onset of disease, especially in humans. A ground-breaking new system has been developed to overcome this challenge, in which "cerebral organoids" that resemble the human brain can be cultured in a dish. Importantly, these cerebral organoids can be generated from a patient's own cells, so any genetic contributions to disease can be directly modeled. While the utility of studying these organoids is far-reaching, our proposal seeks to address a current limitation of cerebral organoid technology, which is that these organoids are likely not as well compartmentalized as the human brain. So that cerebral organoids can serve as a more robust model system to study human neurodevelopmental disorders, we have designed experimental strategies that are aimed at producing organoids that are properly partitioned, which we will use to better model brain deficits in disorders such as ASD.