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Abstract
Byoung-il Bae, Christopher A. Walsh
Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Children's Hospital Boston, Broad Institute of MIT and Harvard, and Departments of Neurology and Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
The human cerebral cortex defines us as who we are. Its development and function underlie complex human cognitive behavior, while its malfunction or degeneration causes countless neurological and psychiatric diseases. It has evolved markedly in humans compared to other animals and, therefore, no animal model truly recapitulates these human-specific features (1). We are currently limited to identifying genetic causes of abnormal brain development and function, observing brain shape and activity through imaging, and examining postmortem brain tissues. You simply cannot analyze human brain development directly. The more we try to model human disease in the mouse?with its miniscule cerebral cortex one-thousandth the size of a human's?the more we recognize the limitations of animal models. Lancaster et al. (2) have provided a major leap by developing a method to grow miniature human brain-like structures (cerebral organoids) from embryonic stem cells in vitro (2). The “minibrains” recapitulate a surprising number of features of human embryonic brain development, heralding a new phase of modeling human disease.
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