Present and future of modeling human brain development in 3D organoids.

Three-dimensional (3D) brain organoids derived from human pluripotent stem cells hold great potential to investigate complex human genetic states and to model aspects of human brain development and pathology. However, the field of brain organoids is still in its infancy, and their use has been limited by their variability and their inability to differentiate into 3D structures with reproducible anatomical organization. Here, starting from a review of basic principles of in vitro 'brain organogenesis', we discuss which aspects of human brain development and disease can be faithfully modeled with current brain organoid protocols, and discuss improvements that would allow them to become reliable tools to investigate complex features of human brain development and disease.