This talk focuses on the mechanisms that promote neural stem cell self-renewal and differentiation in embryonic and adult brain. Using mouse models, video-EEG monitoring, viral techniques, and imaging/electrophysiological approaches, it has been elucidated many of the key transcriptional/epigenetic regulators of adult neurogenesis and showed how aberrant new neuron integration in adult rodent hippocampus contributes to circuit disruption and seizure development. Building on this work, it will be presented recent studies describing how Ca2+ activity mediated genes that regulates the production of aberrant adult-born granule cells. Furthermore, will be presented work using human induced pluripotent stem cells and brain organoid models as approaches to understand brain development and disease. Mutations in one gene, Aristaless-related homeobox (ARX), are of considerable interest, since they are known to cause a common spectrum of neurodevelopmental disorders including epilepsy, autism, and intellectual disability. We have generated cortical and subpallial organoids from patients with poly-alanine expansion mutations in ARX. To understand the nature of ARX mutations in the organoid system, we are currently performing cellular, molecular, and physiological analyses. These data will be presented to gain a comprehensive picture of the pathogenesis of ARX mutations, which has the potential to impact the diagnosis and care of patients with ARX-related epilepsies.