Pluripotent Stem Cell Based Cultures to Study Key Aspects of Human Cerebral Cortex Development

The human brain is a highly organized structure and the cerebral cortex in particular has expanded massively in size during evolution. The cerebral cortex is arranged into layers of specialized neuron subtypes formed during development by orchestrated stem cell maintenance, expansion, fate commitment and differentiation. The cortical neural stem cells generate billions of neurons in a systematic fashion. The mechanisms and their interplay that control most aspects of human brain development are unclear. This is partially due to the ethical and practical challenges associated with analyzing fetal human development. Recent progress into understanding the formation of the human brain has taken advantage of in vitro modeling of corticogenesis using pluripotent cells. Human pluripotent stem cells and procedures developed for their differentiation provided previously unavailable opportunities to study the mechanisms involved in development of the cerebral cortex. These human cell culture models can be applied to address specific biological questions and have been successfully utilized to investigate mechanisms associated, not only with normal brain development, but also neuropsychiatric disorders. Here, we review the recent literature that uses these cell culture models to study human corticogenesis. Then, we discuss the challenges and limitations of the current models.