Normal development of neuronal networks requires a delicate balance of proliferation and differentiation of specific neuronal lineages. Furthermore, it requires the proper migration and integration of these specific neuronal subtypes into the appropriate neuronal circuits. The development of this neuronal circuitry and of the human brain as a whole has intrigued scientists for generations, yet we have not been able to explore the development of human-specific neural networks because of the limitations of current methodologies for investigating the human brain and disorders that affect it. A substantial portion of our understanding of the processes underlying normal brain development comes from our study of neurodevelopmental disorders, in which such critical developmental pathways are disrupted. However, the emerging use of human induced pluripotent stem cells (hiPSCs) can reproduce the disease-altered trajectory of early brain development while retaining a patient’s unique genetic signature, enabling us to disentangle the contribution of genetic and non-genetic factors to the construction or normal and diseased neuronal circuitry.
