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Development. 2016 Aug 1;143(15):2732-40. doi: 10.1242/dev.133066. Epub 2016 Jun 10.

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

Author information

1
The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China The State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
2
The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
3
The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
4
The State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China jwjiao@ioz.ac.cn.

Abstract

Disrupted in schizophrenia 1 (DISC1) is known as a high susceptibility gene for schizophrenia. Recent studies have indicated that schizophrenia might be caused by glia defects and dysfunction. However, there is no direct evidence of a link between the schizophrenia gene DISC1 and gliogenesis defects. Thus, an investigation into the involvement of DISC1 (a ubiquitously expressed brain protein) in astrogenesis during the late stage of mouse embryonic brain development is warranted. Here, we show that suppression of DISC1 expression represses astrogenesis in vitro and in vivo, and that DISC1 overexpression substantially enhances the process. Furthermore, mouse and human DISC1 overexpression rescued the astrogenesis defects caused by DISC1 knockdown. Mechanistically, DISC1 activates the 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. In summary, our results demonstrate that DISC1 regulates astrogenesis by modulating RAS/MEK/ERK signaling via RASSF7 and provide a framework for understanding how DISC1 dysfunction might lead to neuropsychiatric diseases.

KEYWORDS:

Astrogenesis; Cortical development; DISC1; MAP kinase; RAS/MEK/ERK signaling; RASSF7

PMID:
27287808
DOI:
10.1242/dev.133066
[Indexed for MEDLINE]
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