Genetically altered mice are used widely to model human diseases, but as the organization of the human brain is so much more complicated than that of a rodent, brain development diseases have not been tackled. Juergen Knoblich and colleagues have developed an alternative model, a three-dimensional organoid culture system, using human pluripotent stem cells, that recapitulates several aspects of human brain development. The system mimics the temporal development of neuronal subtypes and the organization of the tissue into layers. In proof-of-principle experiments the authors produce a microcephaly model using patient-derived induced pluripotent stem cells and describe defects in neuronal differentiation not previously observed in rodent models.
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