Abstract: The cerebral cortex is the outermost layer of the brain responsible for complex mental tasks such as perception, motor planning and decision making. Detailed knowledge of the constituent cell types, and their local connectivity, is crucial to understand how the cortex operates in health and disease. This talk will consider three main questions related to the development of cortical circuits. First, what is the correspondence between molecular and morphoelectric cell types? In particular, I will discuss the development of Patch-seq for multimodal profiling of single cell morphology, physiology and gene expression, and its application to characterize cell types in the cortex. Second, what is the role of cell lineage in shaping local cortical microcircuits? I will show that excitatory cortical neurons derived from a common progenitor give rise to diverse transcriptomic cell types which form precise, layer-specific synaptic connections with one another. Lastly, can we model human cortical areal specification in vitro? My preliminary data shows that modulation of the retinoic acid signaling pathway during forebrain induction can alter the fate specification of human cortical progenitors using a human induced pluripotent stem cell–derived cerebral organoid model. Taken together, my work suggests that there is a predefined developmental program for the assembly of functional cortical circuits. My future lab will continue to investigate the fundamental mechanisms shaping the development of cortical circuits, and how abnormal circuit development contributes to human neurodevelopmental and neuropsychiatric disorders.