کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4321874 | 1291659 | 2010 | 16 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development](/preview/png/4321874.png)
SummaryThe 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.
► Description of a new DISC1-interacting protein in neural development
► Regulation of DISC1 into Wnt signaling and neural progenitor development
► Dixdc1 as an integrator of DISC1 into Wnt and non-Wnt signaling pathways
► Cyclin-dependent kinase 5-mediated regulation of Dixdc1 in neuronal migration
Journal: - Volume 67, Issue 1, 15 July 2010, Pages 33–48