Neuron
Volume 67, Issue 1, 15 July 2010, Pages 33-48
Journal home page for Neuron

Article
Dixdc1 Is a Critical Regulator of DISC1 and Embryonic Cortical Development

https://doi.org/10.1016/j.neuron.2010.06.002Get rights and content
Under an Elsevier user license
open archive

Summary

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.

Highlights

► 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

MOLNEURO
DEVELOPMENT

Cited by (0)