Multiple lines of evidence suggest that the developing human neocortex is particularly susceptible to genetic risk for neuropsychiatric disease, including autism spectrum disorder (ASD) and schizophrenia (see our Nat. Med. Review
). We have found that de novo variants causing high risk for ASD are enriched in genes co-expressed during early neurogenesis in human cortex and that those processes are recapitulated in our human neural stem models (Neuron, 2014)
. More recently we also observed that genetic risk for schizophrenia appears to act in processes and cell types enriched in the germinal zone (GZ) of the human neocortex, which harbors neural progenitors and early-born neurons. Notably, genetic variation associated with human cognitive performance is also preferentially enriched in the GZ (Cell, 2018)
. We are interested in using multiple approaches including gene expression, chromatin accessibility profiling and genomic engineering in human neural stem cells to identify how corticogenesis and normal brain function are dysregulated in neuropsychiatric disease.