Key Modulator of Schizophrenia Gene Discovered

Researchers from the Massachusetts Institute of Technology recently released a study that builds on the earlier discovery of the disrupted-in-schizophrenia-1 (DISC1) gene. The study discusses the discovery of a key modulator of the DISC1 gene that can impact various stages of brain development.

Co-authors Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and professor, and Karuna Singh, a Picower Institute postdoctoral fellow, examined the gene called Dixdc1, previously pegged as a risk factor for schizophrenia and other mood disorders. The researchers found that Dixdc1—Dix domain containing-1—is a key modulator of DISC1 in the developing brain, “shuttling the DISC1 gene to different molecular signaling pathways during key stages of brain development.” Together, these two genes “activate a signaling cascade that generates neurons,” and then, “when the newly born neurons are migrating to their appropriate destinations, Dixdc1 re-targets DISC1 to interact with another signaling pathway that regulates the structure of neurons while they migrate.”

In an effort to understand whether Dixdc1 regulates neural progenitor proliferation, the team knocked down the expression of Dixdc1 in mice, and then over-expressed DISC1, “which restored normal function even after Dixdc1 was knocked out.”

Writing in Neuron, the researchers conclude: “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.”

According to the researchers, because Dixdc1 has a similar function to DISC1 and helps regulate it, additional studies should be conducted to determine “whether there are distinct mutations in Dixdc1 in particular families that confer risk for psychiatric disease.”