Cerebral organoids: Building brains from stem cells

One of the major challenges facing developmental neurobiology is to understand how a structure as complex as the mammalian brain is put together in a remarkably short time during embryogenesis, starting from a relatively small number of cells. Animal studies have identified numerous regulatory genes and given important insights into how they work, but we still have much to learn. Recent studies indicate that ES cells possess a remarkable ability to self-organize into structures, known as cerebral organoids, that closely resemble the normal embryonic forebrain. This emerging technology represents a new and potentially powerful tool to help unravel normal developmental mechanisms, complementing animal studies. Here, we provide an overview of key steps in brain development, concentrating on the forebrain. We describe how techniques for the production of cerebral organoids have evolved, and provide detailed protocols for growing and analyzing cerebral organoids from mouse pluripotent stem cells (PSCs).