Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development
Name
Singh-2010-Dixdc1 Is a Critical.pdf
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Author(s)
Singh, Karun K.
Ge, Xuecai
Mao, Yingwei
Drane, Laurel
Meletis, Konstantinos
Samuels, Benjamin A.
Tsai, Li-Huei
Date Issued
July 2010
Journal
Neuron
Publisher
Elsevier
Citation
Singh, Karun K., Xuecai Ge, Yingwei Mao, Laurel Drane, Konstantinos Meletis, Benjamin A. Samuels, and Li-Huei Tsai. “Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development.” Neuron 67, no. 1 (July 15, 2010): 33–48. © 2010 Elsevier Inc.
Version
Final published version
Abstract
The psychiatric illness risk gene Disrupted in Schizophrenia-1 (DISC1) plays an important role in brain development; however, it is unclear how DISC1 is regulated during cortical development. Here, we report that DISC1 is regulated during embryonic neural progenitor proliferation and neuronal migration through an interaction with DIX domain containing-1 (Dixdc1), the third mammalian gene discovered to contain a Disheveled-Axin (DIX) domain. We determined that Dixdc1 functionally interacts with DISC1 to regulate neural progenitor proliferation by co-modulating Wnt-GSK3β/β-catenin signaling. However, DISC1 and Dixdc1 do not regulate migration via this pathway. During neuronal migration, we discovered that phosphorylation of Dixdc1 by cyclin-dependent kinase 5 (Cdk5) facilitates its interaction with the DISC1-binding partner Ndel1. Furthermore, Dixdc1 phosphorylation and its interaction with DISC1/Ndel1 in vivo is required for neuronal migration. Together, these data reveal that Dixdc1 integrates DISC1 into Wnt-GSK3β/β-catenin-dependent and -independent signaling pathways during cortical development and further delineate how DISC1 contributes to neuropsychiatric disorders.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.neuron.2010.06.002
