Two three-dimensional models of the developing human brain are reported in Nature this week. The systems, which provide the opportunity to study and modify key aspects of brain development in cultured cells, could help researchers to understand normal brain development and the neurodevelopmental origins of certain diseases, such as autism spectrum disorders and schizophrenia.
As the human fetal brain develops, GABAergic neurons migrate from the ventral to the dorsal forebrain, where they make connections and integrate into cortical circuits. In the first of two related papers, Sergiu Pasca and colleagues model this process by creating 3D spheroids resembling either the ventral or the dorsal forebrain cells that they subsequently assemble in a dish, enabling cell migration and the development of functional human cortical circuits. When the culture system is created using cells from patients with Timothy syndrome - a disorder associated with autism and epilepsy - patterns of cell migration are altered, providing a useful model disease processes at late stages of fetal brain development.
In a second paper, Paola Arlotta and colleagues describe a brain organoid system that can be maintained in culture for over nine months, providing a window to analyse relatively late events of neuronal maturation. These ‘brain-like’ clusters of cells contain a broad diversity of cell types, some of which form spontaneously active neuronal networks. Intriguingly, because the organoids contain various retinal cells, the activity of the neuronal networks could be manipulated using light. Optogenetics, where light is used to control the activity of cells that have been altered to express light-sensitive proteins, has become a widely used tool in neuroscience research. This system, by contrast, could potentially offer an approach for controlling neuronal activity without recourse to genetic modification.