Disrupted in Schizophrenia 1 Regulates Neuronal Progenitor Proliferation via Modulation of GSK3β/β-Catenin Signaling

The Disrupted in Schizophrenia 1 (DISC1) gene is disrupted by a balanced chromosomal translocation (1; 11) (q42; q14.3) in a Scottish family with a high incidence of major depression, schizophrenia, and bipolar disorder. Subsequent studies provided indications that DISC1 plays a role in brain develo...

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Main Authors: Mao, Yingwei (Contributor), Ge, Xuecai (Contributor), Frank, Christopher Lee (Contributor), Madison, Jon M. (Author), Koehler, Angela Nicole (Author), Doud, Mary Kathryn (Author), Tassa, Carlos (Author), Berry, Erin M. (Author), Soda, Takahiro (Contributor), Singh, Karun K. (Contributor), Biechele, Travis (Author), Petryshen, Tracey L. (Author), Moon, Randall T. (Author), Haggarty, Stephen J. (Author), Tsai, Li-Huei (Contributor)
Other Authors: Harvard University- (Contributor), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Contributor), Picower Institute for Learning and Memory (Contributor)
Format: Article
Language:English
Published: Elsevier, 2015-03-25T16:00:37Z.
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Online Access:Get fulltext
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042 |a dc 
100 1 0 |a Mao, Yingwei  |e author 
100 1 0 |a Harvard University-  |e contributor 
100 1 0 |a Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences  |e contributor 
100 1 0 |a Picower Institute for Learning and Memory  |e contributor 
100 1 0 |a Tsai, Li-Huei  |e contributor 
100 1 0 |a Mao, Yingwei  |e contributor 
100 1 0 |a Ge, Xuecai  |e contributor 
100 1 0 |a Frank, Christopher Lee  |e contributor 
100 1 0 |a Soda, Takahiro  |e contributor 
100 1 0 |a Singh, Karun K.  |e contributor 
700 1 0 |a Ge, Xuecai  |e author 
700 1 0 |a Frank, Christopher Lee  |e author 
700 1 0 |a Madison, Jon M.  |e author 
700 1 0 |a Koehler, Angela Nicole  |e author 
700 1 0 |a Doud, Mary Kathryn  |e author 
700 1 0 |a Tassa, Carlos  |e author 
700 1 0 |a Berry, Erin M.  |e author 
700 1 0 |a Soda, Takahiro  |e author 
700 1 0 |a Singh, Karun K.  |e author 
700 1 0 |a Biechele, Travis  |e author 
700 1 0 |a Petryshen, Tracey L.  |e author 
700 1 0 |a Moon, Randall T.  |e author 
700 1 0 |a Haggarty, Stephen J.  |e author 
700 1 0 |a Tsai, Li-Huei  |e author 
245 0 0 |a Disrupted in Schizophrenia 1 Regulates Neuronal Progenitor Proliferation via Modulation of GSK3β/β-Catenin Signaling 
260 |b Elsevier,   |c 2015-03-25T16:00:37Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/96175 
520 |a The Disrupted in Schizophrenia 1 (DISC1) gene is disrupted by a balanced chromosomal translocation (1; 11) (q42; q14.3) in a Scottish family with a high incidence of major depression, schizophrenia, and bipolar disorder. Subsequent studies provided indications that DISC1 plays a role in brain development. Here, we demonstrate that suppression of DISC1 expression reduces neural progenitor proliferation, leading to premature cell cycle exit and differentiation. Several lines of evidence suggest that DISC1 mediates this function by regulating GSK3β. First, DISC1 inhibits GSK3β activity through direct physical interaction, which reduces β-catenin phosphorylation and stabilizes β-catenin. Importantly, expression of stabilized β-catenin overrides the impairment of progenitor proliferation caused by DISC1 loss of function. Furthermore, GSK3 inhibitors normalize progenitor proliferation and behavioral defects caused by DISC1 loss of function. Together, these results implicate DISC1 in GSK3β/β-catenin signaling pathways and provide a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders. 
520 |a National Alliance for Research on Schizophrenia and Depression (U.S.) (Young Investigator Award) 
520 |a Natural Sciences and Engineering Research Council of Canada (Postdoctoral Award) 
520 |a Human Frontier Science Program (Strasbourg, France) (Fellowship) 
520 |a Singleton Fellowship 
520 |a National Institutes of Health (U.S.) (Grant NS37007) 
546 |a en_US 
655 7 |a Article 
773 |t Cell