Haploinsufficiency describes a case in which one of two copies of a gene is mutated and the remaining copy is insufficient to maintain normal function; this mechanism is likely acting in many cases of de novo mutations occurring in autism spectrum disorder (ASD). In the current project, Daniel Geschwind’s team aims to utilize enhancer-targeting gene activation methods to correct the effect of these mutations; stem cell–derived cortical spheroids will be used to comprehensively visualize the development of neuronal subtypes at the cellular and molecular level. This study will enhance our understanding of how haploinsufficiency in ASD genes impacts neuronal development and provide a proof-of-principle for gene activation as a therapeutic intervention.