In the developing cortex, most migrating neural cells are post mitotic. In our experiments, neuronal differentiation is rapidly initiated, and both NES-positive and βIII-tubulin-positive migrating neural cells can be detected. Our observations do not necessarily imply that abnormal in utero neural migration leads to SZ. Although increased SZ hiPSC NPC migration in the scratch assay seems inconsistent with our observation of decreased migration across three neural migration assays, scratch assays more accurately model wound healing rather than neural migration, implying that the defect in SZ hiPSC NPCs lies not in motility but in cellular adhesion. Many of the cellular migration genes decreased in SZ hiPSC NPCs, including NCAM, NRXNs and NLGNs, are also required for synaptic adhesion; aberrant migration of SZ hiPSC NPCs may arise from the very same mechanisms leading to decreased neuronal connectivity in SZ neurons. The further perturbation, rather than amelioration, of SZ neurosphere migration by the antipsychotic loxapine suggests that the relationship between synaptic function and migration is not straightforward.
