Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo

Brain development is an extraordinarily complex process achieved through the spatially and temporally regulated release of key patterning factors. In vitro neurodevelopmental models seek to mimic these processes to recapitulate the steps of tissue fate acquisition and morphogenesis. Classic two-dimensional neural cultures present higher homogeneity but lower complexity compared to the brain. Brain organoids instead have more advanced cell composition, maturation and tissue architecture. They can thus be considered at the interface of in vitro and in vivo neurobiology, and further improvements in organoid techniques are continuing to narrow the gap with in vivo brain development. Here we describe these efforts to recapitulate brain development in neural organoids and focus on their applicability for disease modeling, evolutionary studies and neural network research.