Understanding Primate Brain Development Using Stem Cell Systems

Variations in cerebral cortex size and complexity are thought to contribute to differences in cognitive ability between humans and other animals. We are using primate stem cell systems to understand the cellular and molecular mechanisms underlying species differences in cerebral cortex development. Directed differentiation to cerebral cortex of human and non-human primates pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems enables comparative studies of neurogenesis in different species, including chimpanzee and macaque. Using these approaches, we have identified mechanisms for controlling cerebral cortex size that are regulated cell-autonomously, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output. We are using a range of methods, including single cell RNA sequencing and comparative genomics, to identify candidate genes and pathways that regulate the output of each cortical progenitor cell, and thus contribute to species differences in brain size.