DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7

Disrupted in Schizophrenia1 (DISC1) is known as a high susceptibility gene of schizophrenia. More recent studies have suspected that schizophrenia may be caused by glia defects and dysfunction. However, there is no direct evidence between schizophrenia gene DISC1 and gliogenesis defects. Thus, a precise understanding of DISC1 (a ubiquitously expressed brain protein) on astrogenesis in the late stage of mouse embryonic brain development needs to be investigated. Here, we show that suppression of DISC1 expression represses astrogenesis in vitro and in vivo, whereas DISC1 overexpression substantially enhances the process. Furthermore, mouse and human DISC1 overexpression rescued astrogenesis defects caused by DISC1 knockdown. Mechanistically, DISC1 activates RAS/MEK/ERK signaling pathway via direct association with RASSF7. Also, the pERK complex undergoes nuclear translocation and influences the expression of genes related to astrogenesis. Briefly, our results demonstrate that DISC1 regulates astrogenesis by modulating RAS/MEK/ERK signaling via RASSF7 and provide a framework for understanding how DISC1 dysfunction leads to neuropsychiatric diseases.