Assembly of functionally integrated human forebrain spheroids

摘要: The development of the nervous system involves a coordinated succession events including migration GABAergic (γ-aminobutyric-acid-releasing) neurons from ventral to dorsal forebrain and their integration into cortical circuits. However, these interregional interactions have not yet been modelled with human cells. Here we generate three-dimensional spheroids pluripotent stem cells that resemble either or contain glutamatergic neurons. These subdomain-specific can be assembled in vitro recapitulate saltatory interneurons observed fetal forebrain. Using this system, find Timothy syndrome-a neurodevelopmental disorder is caused by mutations CaV1.2 calcium channel-interneurons display abnormal migratory saltations. We also show after migration, functionally integrate form microphysiological system. anticipate approach will useful for studying neural disease, deriving other brain regions assemble circuits vitro.