We also demonstrate that forebrain subdomains derived from hiPSCs and fused in vitro can be used to identify the transcriptional changes associated with interneuron migration and to model disease processes that are otherwise inaccessible. We find that cortical interneurons derived from TS subjects display a cell-autonomous migration defect whereby they move more frequently but less efficiently. Moreover, the TS interneuron defect is rescued by pharmacologically manipulating LTCC. This aberrant interneuron migration, taken together with our previous studies in cortical glutamatergic neurons26,39,40, suggest the presence of abnormal cortical development and function in TS.
