Fikri Birey - In vitro Modeling of Human Cortical Assembly in Health and Disease
From Steven Marzec
Assembly of inhibitory and excitatory neurons into networks represents a critical period in the development of the cerebral cortex during which early principles of circuit formation and function are established. This elaborate process, which involves GABAerrgic interneurons migrating long distances to integrate with glutamatergic neurons, is, when perturbed, often associated with various neuropsychiatric disorders. However, the lack of access to functional tissue precludes mechanistic insights into how early cortical circuits are wired in humans and miswired in disease. I will describe my work towards developing “forebrain assembloids”, a modular, hiPSC-based brain organoid platform that allows for the previously inaccessible aspects of human cortical assembly, such as human cortical migration and network integration, to be studied in vitro. Using hiPSCs derived from patients with a monogenic form of autism, I will demonstrate how the forebrain assembloid system can be used to uncover novel disease phenotypes at the cellular, molecular and network levels and point to novel therapeutic avenues.