Among the many morphological changes that took place during human origins, an expansion in brain volume is conspicuous. My research group use functional genomic approaches to identify candidate loci underlying human-specific features of brain anatomy and a combination of mouse models and induced pluripotent stem cells to validate and understand the functional consequences of mutations within those loci. We recently discovered a novel enhancer containing human lineage-specific mutations that drive elevated expression of the Wnt receptor FZD8 within neural progenitor cells during early corticogenesis, decreasing their cell cycle time, and increasing cell number and overall brain volume. We have also identified changes in lipid metabolism in adipocytes that result in increased production of diacylglycerides essential for the greatly expanded surface area of neural- and glial cell membranes in the human brain. These results, along with those from other groups, highlight the complex interdependence of changes in development and physiology that underlie the evolution of a bigger brain.