{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["De Rienzo G"],"funding":["NICHD NIH HHS","Stanley Center for Psychiatric Research, Broad Institute","Stanley Medical Research Institute","NIMH NIH HHS","NHGRI NIH HHS","National Institutes of Health"],"pagination":["4184-97"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3236629"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(12)"],"pubmed_abstract":["Disc1 is a schizophrenia risk gene that engages multiple signaling pathways during neurogenesis and brain development. Using the zebrafish as a tool, we analyze the function of zebrafish Disc1 (zDisc1) at the earliest stages of brain and body development. We define a \"tool\" as a biological system that gives insight into mechanisms underlying a human disorder, although the system does not phenocopy the disorder. A zDisc1 peptide binds to GSK3β, and zDisc1 directs early brain development and neurogenesis, by promoting β-catenin-mediated Wnt signaling and inhibiting GSK3β activity. zDisc1 loss-of-function embryos additionally display a convergence and extension phenotype, demonstrated by abnormal movement of dorsolateral cells during gastrulation, through changes in gene expression, and later through formation of abnormal, U-shaped muscle segments, and a truncated tail. These phenotypes are caused by alterations in the noncanonical Wnt pathway, via Daam and Rho signaling. The convergence and extension phenotype can be rescued by a dominant negative GSK3β construct, suggesting that zDisc1 inhibits GSK3β activity during noncanonical Wnt signaling. This is the first demonstration that Disc1 modulates the noncanonical Wnt pathway and suggests a previously unconsidered mechanism by which Disc1 may contribute to the etiology of neuropsychiatric disorders."],"journal":["FASEB journal : official publication of the Federation of American Societies for Experimental Biology"],"pubmed_title":["Disc1 regulates both β-catenin-mediated and noncanonical Wnt signaling during vertebrate embryogenesis."],"pmcid":["PMC3236629"],"funding_grant_id":["RO1 MH091115","R01 HD076585","R01 MH091115","R01 HG002995"],"pubmed_authors":["Ma TP","Tsai LH","Pan L","Sive H","De Rienzo G","Moens CB","Bishop JA","Mao Y"],"additional_accession":[]},"is_claimable":false,"name":"Disc1 regulates both β-catenin-mediated and noncanonical Wnt signaling during vertebrate embryogenesis.","description":"Disc1 is a schizophrenia risk gene that engages multiple signaling pathways during neurogenesis and brain development. Using the zebrafish as a tool, we analyze the function of zebrafish Disc1 (zDisc1) at the earliest stages of brain and body development. We define a \"tool\" as a biological system that gives insight into mechanisms underlying a human disorder, although the system does not phenocopy the disorder. A zDisc1 peptide binds to GSK3β, and zDisc1 directs early brain development and neurogenesis, by promoting β-catenin-mediated Wnt signaling and inhibiting GSK3β activity. zDisc1 loss-of-function embryos additionally display a convergence and extension phenotype, demonstrated by abnormal movement of dorsolateral cells during gastrulation, through changes in gene expression, and later through formation of abnormal, U-shaped muscle segments, and a truncated tail. These phenotypes are caused by alterations in the noncanonical Wnt pathway, via Daam and Rho signaling. The convergence and extension phenotype can be rescued by a dominant negative GSK3β construct, suggesting that zDisc1 inhibits GSK3β activity during noncanonical Wnt signaling. This is the first demonstration that Disc1 modulates the noncanonical Wnt pathway and suggests a previously unconsidered mechanism by which Disc1 may contribute to the etiology of neuropsychiatric disorders.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Dec","modification":"2025-07-05T03:05:13.981Z","creation":"2025-07-05T03:05:13.981Z"},"accession":"S-EPMC3236629","cross_references":{"pubmed":["21859895"],"doi":["10.1096/fj.11-186239"]}}