RT Journal Article
SR Electronic
T1 DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 032243
DO 10.1101/032243
A1 Shukun Wang
A1 Qingli Liang
A1 Huimin Qiao
A1 Hong Li
A1 Tianjin Shen
A1 Fen Ji
A1 Jianwei Jiao
YR 2015
UL http://biorxiv.org/content/early/2015/11/19/032243.abstract
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.