PT - JOURNAL ARTICLE AU - Shukun Wang AU - Qingli Liang AU - Huimin Qiao AU - Hong Li AU - Tianjin Shen AU - Fen Ji AU - Jianwei Jiao TI - DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7 AID - 10.1101/032243 DP - 2015 Jan 01 TA - bioRxiv PG - 032243 4099 - http://biorxiv.org/content/early/2015/11/19/032243.short 4100 - http://biorxiv.org/content/early/2015/11/19/032243.full AB - Disrupted in Schizophrenia1 (DISC1) is known as a high susceptibility gene of schizophrenia. More recent studies have connected schizophrenia with glia defects and dysfunction. However, it is unclear whether there is connection between DISC1 and gliogenesis defect. Thus, a precise understanding of DISC1 (a ubiquitously expressed brain protein) on astrogenesis in the late stage of embryonic mouse brain development needs to be deeply 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 knowndown. Mechanistically, DISC1 activates downstream RAS/MEK/ERK signaling pathway via directly associating with the C terminal domain of RASSF7, a RAS association protein. 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.