Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development
Author(s)Singh, Karun K.; Ge, Xuecai; Mao, Yingwei; Drane, Laurel; Meletis, Konstantinos; Samuels, Benjamin A.; Tsai, Li-Huei; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
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.
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