Assembling Tridimensional Brain Models to Study Human Development and Disease
Progress in dissecting the molecular programs underlying human brain development and in understanding neuropsychiatric disorders has been remarkably slow. This is partly due to lack of access to functioning human brain tissue, translating findings in rodent models and unavailability of functionally relevant in vitro models. In my talk, I will describe efforts in my laboratory to derive 3D brain region-specific cultures starting from human pluripotent stem cells. Specifically, I will show how to derive 3D organoids resembling either the dorsal forebrain and containing cortical glutamatergic neurons, or ventral forebrain and containing GABAergic neurons. These subdomain-specific forebrain organoids can be fused in vitro to generate assembloids and recapitulate the saltatory migration of interneurons and to generate functional circuits of the human cerebral cortex. I will also describe work on human gliogenesis and maturation in years long cultures. Lastly, I will demonstrate how our modular 3D platform can be used to model disease and to study the role of voltage gated calcium channels and the consequences of mutations associated with neuropsychiatric disorders.