A spinning culture system prods stem cells to develop into neurons in three dimensions. The culture system is a gelatinous protein-rich mixture that provides both the structural support and nutrients required for neuronal development.
Neurons inside the mini-brains express proteins specific to distinct brain regions, including the forebrain (FOXG1), the dorsal cortex (EMX1), the prefrontal cortex (AUTS2), the hippocampus (NRP2) and the ventral forebrain (NKX2-1).
The mini-brains contain regions, such as a layer of radial glia (left), that are specific to humans and that do not form in mini-brains derived from mouse stem cells (right).
People with a mutation in the CDK5RAP2 gene (top, left) have smaller brains than controls do (bottom, left). Similarly, mini-brains generated from an individual with this mutation (top row) are smaller than those derived from controls (bottom row).