RNA-sequencing of differentiating neuronal progenitor cells (NPCs) developed from the induced pluripotent stem cells (iPSCs) of four different schizophrenia patients and four control subjects revealed a common dysregulation of 1384 mRNAs and 18 miRNA genes, deconstruction of coordinated mRNA, and miRNA–mRNA networks, and the formation of aberrant networks29. The downregulated genes reside within pathways that block neurogenesis, e.g. Notch1 and Rest, while the upregulated genes were found in pathways that initiate neural development, including master genes, such as Ascl1, Nur77, and RXR, or genes of the Wnt signaling pathway29. ChIPseq revealed that nFGFR1 targets more than 80% of the dysregulated mRNA genes and 31% of dysregulated miRNA genes29. These results indicated an early (preneuronal) genomic etiology of schizophrenia and designated INFS as a common dysregulated mechanism in the Cannon and Keller water-shed model of schizophrenia29,30. Analyses of the differentiated neurons of the same schizophrenia and control iPSC lines revealed impaired migration in 2D cultures31, polarity32, decreased neurite numbers33, reduced synaptic maturation33–36, and decreased activity in the schizophrenia neurons35,36. These changes forecasted a potential disruption of early brain development in schizophrenia.
