Dixcd1 ‘Broad-ens’ Neural Development
While the rate of major psychiatric diseases, such as bipolar disorder, schizophrenia and major depression, affect approximately 3 percent of the human population, one particularly unlucky Scottish family was plagued with a 27 percent rate of occurrence. One family’s burden became a scientist’s treasure, as researchers had an unparalleled opportunity to identify underlying genetic causes of psychiatric disease. Scientists determined that the appearance of family's psychiatric disease co-segregated with a chromosomal translocation disrupting the Disrupted in schizophrenia-1 (DISC1) gene.
Li-Huei Tsai, an Associate Member of the Broad Institute’s Stanley Center for Psychiatric Research, examines the role of DISC1 in cellular signaling –networks involving multiple proteins that when acting cooperatively can perceive and respond to their environment. Although Tsai’s recent research showed that DISC1 is an essential regulator of neural proliferation, the researchers had not determined the molecular mechanisms regulating DISC1 –until now.
Today, a study published by Tsai’s group in Neuron reveals how DISC1 is regulated during neural development. Her group shows that another protein, Disheveled-Axin domain containing-1 (Dixdc1), physically interacts with DISC1. The DISC1-Dixdc1 complex regulates two distinct stages of neural development in two different ways. The DISC1-Dixdc1 dimer (i.e. a protein complex made of two proteins) regulates beta-catenin –an intracellular protein that is integral mediator of embryonic neural development– enhancing embryonic neural cell proliferation. Alternatively, when Dixdc1 and DISC1 associate with another binding partner, creating a trimer (i.e. a protein complex made of three proteins) that is phosphorylated, the complex enhances neural radial migration independent of beta-catenin. Together, these data suggest that DISC1 and Dixcd1 mediate neural development by signaling through multiple intracellular pathways.
Given DISC1’s strong association with psychiatric disease and its established role in neural development, researchers now have a foundation for examining the involvement of disrupted cellular signaling in psychiatric behaviors and disease.