| First Author | Singh KK | Year | 2010 |
| Journal | Neuron | Volume | 67 |
| Issue | 1 | Pages | 33-48 |
| PubMed ID | 20624590 | Mgi Jnum | J:163156 |
| Mgi Id | MGI:4821185 | Doi | 10.1016/j.neuron.2010.06.002 |
| Citation | Singh KK, et al. (2010) Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron 67(1):33-48 |
| abstractText | 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-GSK3beta/beta-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-GSK3beta/beta-catenin-dependent and -independent signaling pathways during cortical development and further delineate how DISC1 contributes to neuropsychiatric disorders. |
