Dixdc1 is a critical regulator of disc1 and embryonic cortical development

Karun K. Singh, Xuecai Ge, Yingwei Mao, Laurel Drane, Konstantinos Meletis, Benjamin A. Samuels, Li Huei Tsai

Research output: Contribution to journalArticle

119 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)33-48
Number of pages16
JournalNeuron
Volume67
Issue number1
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Development
  • Molneuro

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    Singh, K. K., Ge, X., Mao, Y., Drane, L., Meletis, K., Samuels, B. A., & Tsai, L. H. (2010). Dixdc1 is a critical regulator of disc1 and embryonic cortical development. Neuron, 67(1), 33-48. https://doi.org/10.1016/j.neuron.2010.06.002